AP Bio Unit 4 Complete Student Notes Flashcards
Table of Contents Link
Unit 4 Cell Communication Student Notes Page 1
AP Biology
Unit 4
Student Notes
Table of Contents Link
Unit 4 Cell Communication Student Notes Page 2
Unit 4 Student Notes
Table of Contents
A. Cell Communication/Signal Transduction —Pages 3-6
B. Direct Communication Between Cells—Pages 3-5
C. Local Communication Between Cells—Pages 6-8
D. Long Distance Communication Between Cells—Pages 8-10
E. Signal Transduction Pathways—Steps of Cell Signaling—Pages 10-13
F. Types of Receptors—Pages 14-16
G. Feedback Loops—Pages 17-20
H. Introduction to the Cell Cycle—Pages 21-23
I. Stages of the Cell Cycle/Cell Cycle Regulation—Pages 23-30
J. The Cell Cycle and Cancer—Page 30
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Unit 4 Cell Communication Student Notes Page 3
Key Ideas/Enduring Understandings for this unit:
1. Cells communicate by generating, transmitting, receiving, and responding to chemical signals.
2. Timing and coordination of biological mechanisms involved in growth, reproduction, and homeostasis depend
on organisms responding to environmental cues.
3. Heritable information provides for continuity of life.
Cell Communication
Cell-to-Cell Communication
Cell Communication is absolutely essential for multi-cellular organisms to survive and function properly.
Communication is accomplished mainly by chemical means.
Types of cell signaling that can occur between cells or organisms:
Direct
Involves direct physical contact between cells or organisms.
Examples of this type of communication include communication:
A. Across gap junctions between animal cells.
B. Through plasmodesmata that connect adjacent plant cells.
C. Between helper T cells and macrophages.
Illustrative Examples of Communication via Direct Contact Between Cells
Macrophages are a type of white blood cell, of the immune system, that engulf and digest cellular debris, foreign
substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy
body cells on its surface in a process called phagocytosis. These cells play a crucial role in activating the body’s
antibody mediated immune response. This activation is carried out via direct contact with other types of white
blood cells known as helper T cells.
1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen
and displays the pathogen’s antigens on its cell membrane using a protein called the MHC-2 complex. (antigen
presentation). These MHC-2 complexes are found only on phagocytic cells.
2. Macrophages make direct contact with T-helper cells, with binding sites for the specific antigen, and activate
them. The macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells (only
those specific to the antigen).
3. The activated T-helper cells stimulate a specific type of B cell by releasing another signal known as
interleukin-2. Only B cells with receptors for the specific antigen will be activated. These cells can make
antibodies against the antigen causing the trouble. Note: The B cells can also be activated by directly binding to
free antigens.
4. Once the proper B cell type is found and activated, the B cells divide into many exact copies or clones
(monoclonal selection).
5. Most of the cloned B cells then undergo a maturing process and become Plasma cells. The plasma cells are
specialized cells well equipped to produce lots of antibody proteins.
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6. The plasma cells produce lots and lots of antibodies. Each antibody is a protein formed in a very specific shape
to bind to the specific antigen involved in this infection. These antibodies are secreted in large amounts into the
bloodstream where they attach to a specific antigen and mark it for destruction.
7. Once the infection has been dealt with, most of the plasma cells undergo programmed cell death (apoptosis).
Some hang around for quite a while producing more antibodies but eventually they fade away.
8. Some of the activated B cells don’t become plasma cells but instead remain behind as memory cells so that if
the antigen is encountered again, the whole process will be faster and stronger. These activated cells may remain
in the body for years, possibly for life.
The macrophages also help to activate the body’s cell mediated immune response by directly communicating
with Helper T cells.
1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen
and displays the pathogen’s antigens on its cell membrane. (antigen presentation).
2. Macrophages interact with T-helper cells, with binding sites for the specific antigen, and activate them. The
macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells.
3. The Helper-T cells release interleukin-2 which stimulates Cytotoxic T-Cells specific to the antigen.
4. The Cytotoxic T-cells, once stimulated by a T-helper cell, will go through clonal selection. Most of the cloned
cells will become active Cytotoxic T-cells and will search out and destroy any cells in the body that are
displaying the specific antigen involved in this infection. Somatic (body) cells display antigens from intracellular
infections on a protein call the MHC-1 complex. This alerts the Cytotoxic T-Cell to the infection. The MHC-1
complex can interact with a receptor (CD-8) on a Cytotoxic-T cell.
5. Once attached to the infected cell, the Cytotoxic-T cell releases proteins called perforins which kill the
infected cell.
6. Once the infected cells are destroyed, most of the activated T cells, both helper and cytotoxic, will undergo
programmed cell death (apoptosis).
7. A number of activated T-cells remain as Memory cells. These cells will respond to the same antigen in a much
faster manner than occurred during the original infection.
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Local
Often, cells that are near one another communicate through the release of chemical messengers (ligands that can
diffuse through the space between the cells). This type of signaling, in which cells communicate over relatively
short distances, is known as local or paracrine signaling.
Paracrine signaling allows cells to locally coordinate activities with their neighbors. Although they're used in
many different tissues and contexts, paracrine signals are especially important during development, when they
allow one group of cells to tell a neighboring group of cells what cellular identity to take on.
Local signaling may also refer to the communication that occurs at the synapse between two neurons. At the
synapse, the axon of the presynaptic neuron releases neurotransmitters which diffuse across the synapse and bind
to receptors on the post-synaptic neuron.
Illustrative Examples of Communication via the Release of Local Regulators
Neurons--The neuron is the basic working unit of the nervous system. Neurons are specialized cells designed to
transmit information to other nerve cells, muscle cells, or gland cells.
Neuron (Nerve cell) structure:
Cell Body or Soma - This portion of the neuron contains the DNA and organelles of the cell. This structure
helps to produce the proteins and other substances needed throughout the rest of the cell.
Dendrites - These structures receive incoming signals from other neurons. Most neurons have several dendrites
that branch out from the soma like tree branches. The dendrites have ligand-gated ion channel receptors that
interact with neurotransmitters released by other neurons.
Axon – The axon transmits the signal to the next neuron or muscle cell. It typically does this by releasing
neurotransmitters which bond to receptors on the next cell in the chain.
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Synaptic Terminal – This term refers to the end of the axon found at a synapse.
Synapse - This is the gap between neurons or between a neuron and an effector cell.
Neurotransmitter – Neurotransmitters are chemical signals that are produced by the neuron that are used to
transmit the signal across the synapse and to the next neuron. Example neurotransmitters include:
Acetylcholine, Dopamine, Serotonin, Nitric Oxide, Epinephrine, and Norepinephrine.
Neurotransmitters are released from the axon terminal of the Presynaptic neuron.
Neurotransmitters are received by the receptors on the dendrites of the Postsynaptic neuron. Once enough
neurotransmitters bind to the receptors, an action potential/nerve impulse is initiated in the post synaptic neuron.
Neuron Structure
The Synapse
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Morphogens
Morphogens are secreted signaling molecules that diffuse from local sources to form concentration gradients,
which specify multiple cell fates during embryonic development. One of the most famous morphogens is the
Sonic Hedgehog protein. Sonic hedgehog is one of three proteins in the mammalian signaling pathway family
called hedgehog, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best
studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such
as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example
of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form
a concentration gradient and has different effects on the cells of the developing embryo depending on its
concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been
implicated in the development of some cancers.
Quorum Sensing in Bacteria
Unicellular prokaryotes, like bacteria, also possess mechanisms for cell to cell communication. One of the most
important examples of a local signaling mechanism in bacteria is quorum sensing. Quorum sensing (QS) is a
bacterial cell–cell communication process that involves the production, release, detection, and response to
extracellular signaling molecules called autoinducers (AIs). AIs accumulate in the environment as the bacterial
population density increases, and bacteria monitor this information to track changes in their cell numbers and
collectively alter gene expression. QS controls genes that direct activities that are only beneficial when performed
by groups of bacteria acting in synchrony. These genes are only activated when the bacterial density in the local
area is high enough for their actions to be beneficial. Processes controlled by QS include bioluminescence,
sporulation, competence, antibiotic production, biofilm formation, and virulence factor secretion.
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Long Distance
Long distance signaling may occur between cells (in the same organism) that are located far apart or
between two different organisms that are separated by large distances.
Hormones – Hormones are chemical messengers that are released directly into the bloodstream from an
endocrine gland located in one part of the body. The hormones travel through the blood to specific cells (target
cells) that have the appropriate receptor for the hormone. The binding of the hormone to the receptor transmits
the message to the target cell. Hormones are typically composed of either proteins or steroids (lipids).
Pheromones - Pheromones are chemicals capable of acting like hormones outside the body of the
secreting individual, to impact the behavior of the receiving individuals. There
are alarm pheromones, food trail pheromones, sex pheromones, and many others that affect behavior or
physiology. Pheromones are used from basic unicellular prokaryotes to
complex multicellular eukaryotes. Pheromones are usually made from steroids (lipids).
Illustrative Examples of Cellular Communication That Occurs Over Long Distances
Blood Glucose Maintenance
When blood glucose levels rise above the set point range, the pancreas releases the hormone insulin.
Insulin travels throughout the body via the bloodstream. It binds to receptors on numerous types of body cells
like those in the liver and muscles. Once insulin attaches to the receptors, the signal transduction pathway that it
initiates ultimately causes the target cells to absorb glucose from the blood and store it within the cell. This
lowers the blood glucose level.
When blood glucose levels drop below the set point range, the pancreas releases the hormone glucagon.
Glucagon travels throughout the body via the bloodstream. It binds to receptors on numerous types of body cells
like those in the liver and muscles. Once glucagon attaches to the receptors, the signal transduction pathway that
it initiates ultimately causes the target cells to breakdown glucose storage molecules like glycogen and to release
the freed glucose into the bloodstream. This ultimately raises the blood glucose level.
The levels of insulin and glucagon in the bloodstream are regulated by a negative feedback loop.
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Steroid Hormones
Other hormones like testosterone and estrogen are steroid (lipid-based) hormones which are capable of passing
through the cell membrane. Once inside the cell, these hormones bind to intracellular receptors.
The hormone/receptor complex enters the nucleus and acts as a transcription factor. This transcription factor causes
the activation of a specific gene or set of genes.
The responses caused by steroid hormones are typically slower than those caused by protein hormones, but the
responses caused by steroid hormones are typically longer in duration.
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Signal Transduction Pathway
Signal Transduction pathways link signal reception with cellular responses. The pathways usually involve a
group of molecules in a cell that work together to control one or more cell functions, such as cell division or cell
death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated
until the last molecule is activated and the cell function is carried out.
Ligand – Ligand is another name for a signaling molecule.
The ligand binds to the receptor protein on the cell membrane (if the ligand is made of protein) or inside the cell
(if the ligand is a steroid/lipid).
The attachment of the ligand to the receptor causes a conformational shape change in the receptor protein that
sets in motion the signal transduction pathway.
Different ligands can initiate different responses. The same ligand can initiate different responses in different
types of cells because these cells contain different signal transduction pathways.
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Three parts to the pathway:
Reception – Reception begins when the signaling molecule binds to the ligand binding domain of
a membrane receptor protein.
The receptors are very specific to a particular signaling molecule. The signal molecule must fit into
the receptor like a substrate fits into the active site of an enzyme. Different cells possess different
receptors and are capable of interacting with different signaling molecules. Most receptors extend
outside the cell membrane (extracellular receptors) because most signaling molecules are composed
of proteins This means that they are too large and charged to enter the cell. After the signal
molecule attaches to the receptor, the intracellular domain of the receptor protein (the part of the
receptor protein that extends through the membrane and into the cytoplasm) undergoes a
conformation change (change in shape). This process helps to move the signal from outside to
inside the cell and initiates the transduction of the signal.
It is important to note that mutations in the genes that code for any of the domains (sections)
of the receptor proteins or in any component/protein of the signaling pathway may affect the
other downstream components of the pathway by altering the subsequent transduction of the
signal.
Chemicals which interfere any component of the signaling pathway may activate or inhibit the
pathway.
Note that steroid/lipid-based hormones bind to receptors located inside the cell (intracellular
receptors).
Transduction -- Since signaling systems need to be responsive to small concentrations of chemical
signals and act quickly, cells often use a multi-step pathway that transmits the signal quickly, while
amplifying the signal to numerous molecules at each step. Steps in the signal transduction pathway
often involve the addition or removal of phosphate groups which results in the activation of
proteins. Enzymes that transfer phosphate groups and energy from ATP to a protein are
called protein kinases. Many of the relay molecules in a signal transduction pathway are protein
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kinases and often act on other protein kinases in the pathway. Often this creates a phosphorylation
cascade, where one enzyme phosphorylates another, which then phosphorylates another protein,
causing a chain reaction. Also important to the phosphorylation cascade are a group of proteins
known as protein phosphatases. Protein phosphatases are enzymes that can rapidly remove
phosphate groups from proteins (dephosphorylation) and thus inactivate protein kinases. Protein
phosphatases are the “off switch” in the signal transduction pathway.
A benefit of transduction is that a small number of ligands (signals) can help to activate a large
number of molecules at the end of the pathway. We can say that transduction often amplifies a
chemical signal along the signal transduction pathway.
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Response – The response is the action the signal was meant to initiate and/or regulate. A signal transduction
pathway regulates one or more cellular activities. Potential responses to cell signals include:
The opening of an ion channel—Example: The opening of ligand gated ion channels on neurons in
response to the binding of neurotransmitters.
The breakdown of a substance in a cell—The breakdown of glycogen in the liver stimulated by the binding
of epinephrine to receptors on the liver cells.
The synthesis of enzymes or proteins (gene expression)—Rising levels of ethylene gas cause the
production and activation of enzymes that cause the ripening of fruits.
The turning on/off of certain genes (gene regulation)—The expression of the SRY gene triggers the
development of the male sexual development pathway.
Hox genes are a group of related genes that specify regions of the body plan of an embryo along the head-tail
axis of animals. Hox genes actually code for transcription factors which cause the expression of genes that
encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct
places of the body. For example, Hox genes in insects specify which appendages form on a segment (e.g.
legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae
that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not
form the actual segments themselves.
An analogy for the Hox genes can be made to the role of a play director that calls which scene the actors
should carry out next. If the play director calls the scenes in the wrong order, the overall play will be
presented in the wrong order. Similarly, mutations in the Hox genes can result in body parts and limbs in the
wrong place along the body. Like a play director, the Hox genes do not act in the play or participate in limb
formation themselves.
Cell Growth/Reproduction—Cytokines are cell signals that regulate gene expression and stimulate cell
replication and division.
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AP Biology
Cell Communication Part 2
Types of Signal Receptors
G- Protein Linked Receptor
G-Protein-Linked Receptors-- These extracellular receptors are the largest and most diverse group of
receptors found in eukaryotes. G-protein-linked receptors may bind ligands which range from odor
molecules to pheromones to hormones to neurotransmitters.
Once a ligand binds to the G-protein-linked receptor, a GTP molecule is attached to the alpha subunit of the
receptor. The alpha subunit then breaks free (the conformational change) and activates a protein/enzyme
which creates multiple secondary messengers like cAMP. The job of a secondary messenger is to transmit
the signal from just inside the cell membrane throughout the rest of the cytoplasm.
Secondary messengers stimulate the proteins of the signal transduction pathway and the creation of multiple
secondary messengers in response to one ligand. This starts the amplification (spreading of the signal
throughout the cell) of the signal.
A limitation of individual G-protein-linked receptors is that they can only activate one signal transduction
pathway and thus bring about one, specific response.
Receptor Tyrosine Kinases
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Receptor Tyrosine Kinase (RTK)-- These cell surface (extracellular) receptors bind and respond to growth factors
and other locally released proteins that are present at low concentrations. RTKs play important roles in
the regulation of cell growth, differentiation, and survival. Insulin receptors are an example of this category of
extracellular receptors. When signaling molecules bind to RTKs, they cause neighboring RTKs to associate with
each other, forming cross-linked dimers. Cross-linking activates the tyrosine kinase activity in these RTKs
through phosphorylation. Each RTK in the dimer phosphorylates multiple tyrosines on the other RTK. This
process is called cross-phosphorylation.
This allows receptor tyrosine kinases to activate multiple signal transduction pathways at a time and stimulate
multiple cellular responses.
RTKs are often involved with growth/emergency repair processes.
Ligand Gated Ion Channels
Certain cells, commonly called excitable cells, are unique because of their ability to generate electrical signals.
Although several types of excitable cells exist — including neurons, muscle cells, and touch receptor cells — all
of them use ligand-gated ion channel receptors to convert chemical or mechanical messages into electrical
signals.
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Intracellular Receptors
These receptors are mostly for steroids. Since these molecules are lipids, they don’t need receptor
proteins on the cell membrane. They travel into the cell by diffusing across the phospholipid bi-layer.
Steroids such as estrogen and testosterone are able to cross the cell membrane (because of their lipid
nature) and interact with intracellular receptors.
The steroid and receptor complex then enters the nucleus and acts as a gene regulatory protein. These
proteins can stimulate the transcription of specific genes. Essentially, they can “turn on” specific
genes. Because they can enter the cell and stimulate specific genes, steroids can often stimulate
responses that are slower, but more sustained than those caused by protein-based signals that interact
with extracellular receptors.
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Feedback Loops
Homeostasis--a property of an organism or system that helps it maintain its parameters (temperature, blood glucose levels,
blood calcium levels, heart rate, blood pressure, etc..) within a normal (fairly constant) range of values. One of the main
functions of the endocrine system is to help maintain homeostasis.
Feedback loops are mechanisms used by organisms to maintain their internal environments and respond to internal and
external environmental changes.
Negative Feedback Loop—A negative feedback loop occurs in biology when the product of a reaction leads to a decrease in
that reaction. In this way, a negative feedback loop brings a system closer to a target set point of stability or homeostasis.
Negative feedback loops are responsible for the stabilization of a system, and ensure the maintenance of a steady, stable
internal state. The response of the regulating mechanism is opposite to the output of the event. Another way of thinking
about negative feedback loops is that if a system is perturbed/disturbed, negative feedback mechanisms return the system to
its target set point. These mechanisms operate on both the molecular and cellular levels. Examples in the human body
include: Thermoregulation; Maintenance of blood glucose levels; Maintenance of blood calcium levels.
Components of a Negative Feedback Loop
Stimulus—a change in a variable away from the set point range.
Receptor—senses a change in a variable.
Control Center—compares the changes to the set point range. Sends out either nervous or endocrine signals to
effectors which will reverse the change back toward the set point. In many human feedback loops, the control
center is the hypothalamus.
Effector—makes adjustments to the variable.
Response—change in the variable caused by the effector.
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Idealized Negative Feedback Loop
Negative Feedback Loop for Blood Glucose Maintenance
Insulin is normally secreted by the beta cells (a type of islet cell) of the pancreas. The stimulus for insulin secretion is a HIGH
blood glucose...it's as simple as that! Although there is always a low level of insulin secreted by the pancreas, the amount
secreted into the blood increases as the blood glucose rises. Similarly, as blood glucose falls, the amount of insulin secreted by
the pancreatic islets goes down.
As can be seen in the picture below, insulin has an effect on a number of cells, including muscle, red blood cells, and fat
cells. In response to insulin, these cells absorb glucose out of the blood, having the net effect of lowering the high blood
glucose levels into the normal range.
Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin...except in the opposite
direction. If blood glucose is high, then no glucagon is secreted.
When blood glucose goes LOW, however, (such as between meals, and during exercise) more and more glucagon is secreted.
Like insulin, glucagon has an effect on many cells of the body, but most notably the liver.
The effect of glucagon is to make the liver release the glucose it has stored in its cells into the bloodstream, with the net effect
of increasing blood glucose. Glucagon also induces the liver (and some other cells such as muscle) to make glucose out of
building blocks obtained from other nutrients found in the body (eg, protein).
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Positive Feedback Loops
Positive Feedback Loop--A positive feedback loop occurs in nature when the product of a reaction leads
to an increase in that reaction. If we look at a system in homeostasis, a positive feedback loop moves a
system further away from the target of equilibrium. It does this by amplifying the effects of a product or
event and occurs when something needs to happen quickly. Breast milk production and release—The act
of suckling by an infant causes the pituitary gland to release prolactin, which leads to milk production;
more suckling leads to more prolactin release, which in turn leads to more lactation. This is a positive
feedback system as the product (milk) produces more suckling and more hormone. When the child is no
longer breast feeding, the prolactin drops off and milk production goes down.
A baby pushing against the cervix causes the cervix to stretch. The stretching causes nerve impulses to
travel to the brain. This stimulates the release of the hormone oxytocin by the pituitary gland. The
oxytocin binds to receptors on the cells of the uterine wall and stimulates it to contract. This causes the
cervix to stretch even more, which causes the release of more oxytocin, which causes more frequent and
stronger uterine contractions.
A ripening apple releases the hormone known as ethylene gas. This hormone stimulates neighboring
apples to ripen. This causes the release of more ethylene gas which causes even more apples to ripen.
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Positive Feedback Loop for Childbirth
Positive Feedback Loop for Fruit Ripening
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AP Biology
Introduction to the Cell Cycle
ALL cells undergo three basic processes associated with reproduction/division.
• Replication of the DNA within the parent cell. This occurs in what is referred to as the “S phase”.
(Synthesis phase). Each cell must have a complete copy of the DNA. The DNA in each cell is
identical.
• Replication of any items that are in the cytoplasm, such as ribosomes and organelles (only in eukaryotic
cells).
• Division of the cytoplasm and cell membrane. This is referred to as cytokinesis.
Binary Fission (Prokaryotic Fission) in Prokaryotes
This is the process of Reproduction/Replication in prokaryotes (bacteria). Binary Fission is a type of asexual
reproduction. The process does not create any genetic diversity.
DNA replication (S phase) starts at a single “origin of replication” and works around the entire single, circular
chromosome. This results in two identical circular chromosomes in the nucleoid region.
This is followed by the production of a cleavage furrow in the cell membrane (cytokinesis) to produce 2 new
cells, that are referred to as clones.
The cleavage furrow is produced using actin and myosin (protein) microfilaments of the cytoskeleton.
The two resulting cells are called clones because they possess 100% identical DNA strands.
Biologists think that binary fission evolved into Mitosis as the DNA content of cells increased dramatically.
Binary Fission
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Vocabulary Related to Eukaryotic Cell Division
Cell Cycle—The life cycle of the cell. This includes times in which the cell grows and carries out its designated function(s)
and times in which it replicates its DNA and divides. The cell cycle is a highly regulated series of events for the growth
and development of cells. The cell cycle is a highly regulated series of events for the growth and development of cells.
Parent or Mother cell—The original cell that begins to divide.
Daughter cells—The two identical cells that result from the division of the mother cell. These cells are genetically identical
clones.
Genome – The entire genetic material (DNA) for an organism or cell.
In humans, the genome length is about 2 m or 7 ft. per cell.
Chromatin – This term refers to DNA in its loose, non-chromosome, formation. In this state DNA can be replicated and
transcribed.
Chromosomes – This term refers to DNA in its tightly coiled state. Chromosomes are only present in a cell just before
and during the process of cell division.
Somatic cells (“soma” means body) - These are normal body cells.
These are the cells that make up the majority of an organism.
Their chromosomal content is 2n or diploid. This means that these cells have two copies of each type of
chromosome. (They get half “n”from the “mother”; half “n” from the “father”.)
For humans cells, the diploid number is 46 chromosomes = 2n. (n= 23 in the egg; n=23 in the sperm.)
Germ cells- These are the only cells in the human body that are capable of doing meiosis. Meiosis forms four haploid
gametes (sperm or egg cells) from each diploid germ cell.
Meiosis is the process of making haploid sperm or eggs.
Histones
These are the proteins that help DNA coil up “condense” to form chromosomes during cell division.
When DNA is wrapped around these histones, the whole combined structure is referred to as a nucleosome.
The histones also play an important role in gene regulation.
Sister Chromatids--A portion of the whole “duplicated” chromosome.
This term refers to half of a duplicated or bivalent chromosome. Duplicated or bivalent chromosomes look like
an “X”.
The two halves are held together at the centromere , which is a group of proteins in a constricted portion of the
chromosome.
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The “homologous chromosomes” pictured above are bivalent or duplicated. Homologous means that the
two chromosomes are of the same type and control the same traits.
Mitosis vs. Meiosis
Mitosis – This process refers to ordinary cell division. Almost all cells in the body carry out mitosis. After
mitosis and cytokinesis, one mother cell forms two identical daughter cells. Mitosis is a form of cloning. Its
functions include repair of tissue damage, replacement of old/worn out cells, growth, and asexual reproduction (in
some organisms).
.
Meiosis – Meiosis is the process of forming haploid gametes from diploid germ cells. One germ cell forms
four haploid gametes after meiosis. The four gametes are genetically different from each other. Meiosis is an
important source of genetic variation.
AP Biology
Stages of the Cell Cycle/Cell Cycle Regulation
Phases of the Eukaryotic Cell Cycle:
Interphase
Cells spend up to 90% of their existence in Interphase. Interphase is not part of mitosis. It is the time
during the cell division in which the cell carries out ordinary, everyday growth, activity, and/or repair of
the cell.
Interphase consists of three parts:
G1 (Primary or “first” growth)
During this stage ordinary, everyday growth, activity, and/or repair of the cell takes place.
Organelles begin replicating.
The first checkpoint of the cell cycle occurs at the end of G1.
A checkpoint is one of several points in the eukaryotic cell cycle at which the
progression of a cell to the next stage in the cycle can be halted until conditions are
favorable.
The cell will only pass the G1 checkpoint if it is an appropriate size and has adequate
energy reserves. At this point, the cell also checks for DNA damage. A cell that does not
meet all the requirements will not progress to the S phase. The cell can halt the cycle and
attempt to remedy the problematic condition, or the cell can advance into G(inactive)
0
phase and await further signals when conditions improve.
.
S (synthesis)
During S phase, DNA replicates or is synthesized.
In humans, the 46 single chromatid chromosomes are replicated to form 46 bivalent
chromosomes.
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G2 (Secondary or “second” growth)
During G2, the organelles enlarge and are replicated.
The newly synthesized DNA is checked for errors.
The second checkpoint occurs at the end of G2. The Gcheckpoint bars entry into the
2
mitotic phase if certain conditions are not met. As with the Gcheckpoint, cell size and
1
protein reserves are assessed. However, the most important role of the Gcheckpoint is to
2
ensure that all of the chromosomes have been accurately replicated without mistakes or
damage. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is
halted and the cell attempts to either complete DNA replication or repair the damaged
DNA.
Mitosis- Mitosis ensures the transfer of a complete genome from a parent cell to two genetically identical daughter
cells. Mitosis is technically not “cell division”. Mitosis is a form of nuclear division. It is followed by the process of
cytokinesis which divides the cell or cytoplasm.
Mitosis plays an important role in the processes of growth, tissue repair, and asexual reproduction.
Mitosis occurs in the sequential stages of—Prophase, Metaphase, Anaphase, and Telophase. Note that some textbook
authors choose to divide prophase into two phases (prophase and prometaphase).
Prophase
During prophase, the nuclear envelope is broken down and the centrosomes construct the
spindle apparatus.
The chromatin condenses to form “X” shaped bivalent chromosomes. (Two chromatids.)
Centrioles move toward the poles. Note that plant cells don’t have centrioles.
The spindle fibers begin to attach to each chromosome at a point on the chromosome called
the kinetochore (a part of the centromere).
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Metaphase (“meta” means “middle”)
The chromosomes are pulled toward the middle of the cell and line up on the metaphase
plate. (Middle of cell.)
The third checkpoint occurs at the end of metaphase. The M checkpoint occurs near the
end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle
checkpoint because it determines whether all the sister chromatids are correctly attached to
the spindle microtubules. Because the separation of the sister chromatids during anaphase
is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister
chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of
the cell. As the chromosomes’ kinetochores connect with the spindle apparatus, enzymes
are “turned on”. The enzymes are called Anaphase Promoting Complexes. (APC). When
concentration levels of APC reach the checkpoint level, Anaphase begins. The process
described above is sometimes referred to as the kinetochore signal.
Anaphase (“ana” means “separate”)
Each of the bivalent chromosomes are pulled apart and the two chromatids from each
bivalent chromosome (now referred to as a chromosomes) are pulled towards opposite
poles (ends) of the cell.
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The spindle apparatus is broken down as the two sister chromosomes are “walked” toward
the poles by motor proteins which use ATP as an energy source.
Telophase (“telo” means “last”)
A new nuclear envelope is built around each of the two sets of DNA.
The chromosomes begin to decondense back to their chromatin state.
A cleavage furrow begins to form using actin and myosin microfilaments.
Telophase can be thought of as the opposite of prophase.
Cytokinesis (“Cleavage” means “split”) - This is the division of the cytoplasm.
The cytoplasm and cell organelles are separated to produce two genetically identical daughter cells.
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G0 (Zero growth phase)
The G0 phase is a period in the cell cycle in which cells exist in a quiescent/non-dividing state. G0 phase
is viewed as either an extended G1 phase, where the cell is neither dividing nor preparing to divide, or a
distinct quiescent stage that occurs outside of the cell cycle. G0 is sometimes referred to as a "post-
mitotic" state, since cells in G0 are in a non-dividing phase outside of the cell cycle. Some types of cells,
such as nerve and heart muscle cells, become post-mitotic when they reach maturity (i.e., when they are
terminally differentiated) but continue to perform their main functions for the rest of the organism's life.
These cells will never re-enter the normal cell cycle. Multinucleated muscle cells that do not undergo
cytokinesis are also often considered to be in the G0 stage. On occasion, a distinction in terms is made
between a G0 cell and a 'post-mitotic' cell (e.g., heart muscle cells and neurons), which will never enter
the G1 phase, whereas other G0 cells may. There are cases in which cells in the G0 phase reenter the
normal cell cycle in response to certain environmental cues.
Spindle Apparatus
The spindle apparatus is composed of a network of protein filaments (mostly microtubules).
The construction begins at the centrosome (where the centrioles are) and works toward the chromosomes.
The spindle fibers attach to the kinetochore on the centromere of the replicated chromosomes.
Motor Proteins “walk” the chromosomes/sister chromatids toward the opposite poles (ends) using ATP as a
source of energy.
Non-kinetochore spindles are used to “push” the poles farther apart (to elongate the cell) and to help produce the
cleavage furrow.
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Cell Plate
Centrioles (in animal cells) act as anchorage points for the spindle fibers.
Plant cells DO NOT have centrioles because the cell wall is used as an anchor point for the spindle fibers.
When plant cells divide, a NEW cell wall “Plate” develops, using small segments of cellulose. There is not a
need for a cleavage furrow.
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Regulation “control” of the Cell Cycle.
Regulation is crucial for normal growth and development.
Regulation varies from cell type to cell type.
The most important form of regulation involves protein-based cell signals called Cyclins.
Checkpoints are also important. See the discussion included above for information pertaining to the three
cell cycle checkpoints.
Cyclin Production
The cyclin concentration in a cell increases from S phase until Anaphase.
Cyclins combine with an inactive enzyme known as Cyclin dependent Kinase (CdK) to form an active enzyme
known as Maturation Promoting Factor (MPF). MPF causes the cell to enter mitosis because it phosphorylates the
nuclear lamina and causes the nuclear membrane to begin the process of disintegration.
Cyclins are degraded after Mitosis leaving only CdK behind. Without cyclin, CDK is inactive.
This process essentially resets the “life clock” for the cell.
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The Cell Cycle and Cancer
Cancer (ABNORMAL cell growth/reproduction)
Cancer “creates”abnormally high Cyclin production within cells.
No checkpoints exist within cancerous cells, so there is no density-dependent inhibition.
Cancer cells are considered “immortal” as long as they have oxygen and nutrients.
Angiogenesis occurs – Angiogenesis is the “creation of new blood vessels” to “feed” the tumor.
Cancer cells have active telomerase enzymes present. A telomere is a region of
repetitive sequences at each end of eukaryotic chromosomes in most eukaryotes. Telomeres protect
the end of the chromosome from DNA damage or from fusion with neighboring chromosomes.
Telomeres get shorter with every cell division/DNA replication. There is evidence that the length of
the telomeres may regulate the life expectancy of a cell. When the telomeres get to a certain length,
the cell is programmed to undergo apoptosis (cell death). Telomerase is an enzyme that lengthens the
telomeres. The enzyme is active in fetuses, but is mostly inactivated after birth. Since cancer cells
have active telomerase enzymes, their telomeres don’t shorten. This means that they never have to go
through apoptosis and are essentially immortal.
Normal cells divide between 1 and 100 times each. This varies from cell type to cell type.
If no telomeres are present, the cell will not be able to continue dividing.
Cancer starts with Transformation of the DNA in a cell. (Transformation of telomerase to the “on”
setting.)
Things that can causes this to occur: weak genetic history, trauma, a viral insert of DNA/RNA and/or
repeated carcinogen exposure.
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Unit 4 Cell Communication Student Notes Page 1
AP Biology
Unit 4
Student Notes
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Unit 4 Cell Communication Student Notes Page 2
Unit 4 Student Notes
Table of Contents
A. Cell Communication/Signal Transduction —Pages 3-6
B. Direct Communication Between Cells—Pages 3-5
C. Local Communication Between Cells—Pages 6-8
D. Long Distance Communication Between Cells—Pages 8-10
E. Signal Transduction Pathways—Steps of Cell Signaling—Pages 10-13
F. Types of Receptors—Pages 14-16
G. Feedback Loops—Pages 17-20
H. Introduction to the Cell Cycle—Pages 21-23
I. Stages of the Cell Cycle/Cell Cycle Regulation—Pages 23-30
J. The Cell Cycle and Cancer—Page 30
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Key Ideas/Enduring Understandings for this unit:
1. Cells communicate by generating, transmitting, receiving, and responding to chemical signals.
2. Timing and coordination of biological mechanisms involved in growth, reproduction, and homeostasis depend
on organisms responding to environmental cues.
3. Heritable information provides for continuity of life.
Cell Communication
Cell-to-Cell Communication
Cell Communication is absolutely essential for multi-cellular organisms to survive and function properly.
Communication is accomplished mainly by chemical means.
Types of cell signaling that can occur between cells or organisms:
Direct
Involves direct physical contact between cells or organisms.
Examples of this type of communication include communication:
A. Across gap junctions between animal cells.
B. Through plasmodesmata that connect adjacent plant cells.
C. Between helper T cells and macrophages.
Illustrative Examples of Communication via Direct Contact Between Cells
Macrophages are a type of white blood cell, of the immune system, that engulf and digest cellular debris, foreign
substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy
body cells on its surface in a process called phagocytosis. These cells play a crucial role in activating the body’s
antibody mediated immune response. This activation is carried out via direct contact with other types of white
blood cells known as helper T cells.
1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen
and displays the pathogen’s antigens on its cell membrane using a protein called the MHC-2 complex. (antigen
presentation). These MHC-2 complexes are found only on phagocytic cells.
2. Macrophages make direct contact with T-helper cells, with binding sites for the specific antigen, and activate
them. The macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells (only
those specific to the antigen).
3. The activated T-helper cells stimulate a specific type of B cell by releasing another signal known as
interleukin-2. Only B cells with receptors for the specific antigen will be activated. These cells can make
antibodies against the antigen causing the trouble. Note: The B cells can also be activated by directly binding to
free antigens.
4. Once the proper B cell type is found and activated, the B cells divide into many exact copies or clones
(monoclonal selection).
5. Most of the cloned B cells then undergo a maturing process and become Plasma cells. The plasma cells are
specialized cells well equipped to produce lots of antibody proteins.
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6. The plasma cells produce lots and lots of antibodies. Each antibody is a protein formed in a very specific shape
to bind to the specific antigen involved in this infection. These antibodies are secreted in large amounts into the
bloodstream where they attach to a specific antigen and mark it for destruction.
7. Once the infection has been dealt with, most of the plasma cells undergo programmed cell death (apoptosis).
Some hang around for quite a while producing more antibodies but eventually they fade away.
8. Some of the activated B cells don’t become plasma cells but instead remain behind as memory cells so that if
the antigen is encountered again, the whole process will be faster and stronger. These activated cells may remain
in the body for years, possibly for life.
The macrophages also help to activate the body’s cell mediated immune response by directly communicating
with Helper T cells.
1. A macrophage or other phagocyte engulfs and intracellularly digests (with the help of lysosomes) a pathogen
and displays the pathogen’s antigens on its cell membrane. (antigen presentation).
2. Macrophages interact with T-helper cells, with binding sites for the specific antigen, and activate them. The
macrophages release a cell signal known as interleukin-1 which activates the Helper-T cells.
3. The Helper-T cells release interleukin-2 which stimulates Cytotoxic T-Cells specific to the antigen.
4. The Cytotoxic T-cells, once stimulated by a T-helper cell, will go through clonal selection. Most of the cloned
cells will become active Cytotoxic T-cells and will search out and destroy any cells in the body that are
displaying the specific antigen involved in this infection. Somatic (body) cells display antigens from intracellular
infections on a protein call the MHC-1 complex. This alerts the Cytotoxic T-Cell to the infection. The MHC-1
complex can interact with a receptor (CD-8) on a Cytotoxic-T cell.
5. Once attached to the infected cell, the Cytotoxic-T cell releases proteins called perforins which kill the
infected cell.
6. Once the infected cells are destroyed, most of the activated T cells, both helper and cytotoxic, will undergo
programmed cell death (apoptosis).
7. A number of activated T-cells remain as Memory cells. These cells will respond to the same antigen in a much
faster manner than occurred during the original infection.
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Local
Often, cells that are near one another communicate through the release of chemical messengers (ligands that can
diffuse through the space between the cells). This type of signaling, in which cells communicate over relatively
short distances, is known as local or paracrine signaling.
Paracrine signaling allows cells to locally coordinate activities with their neighbors. Although they're used in
many different tissues and contexts, paracrine signals are especially important during development, when they
allow one group of cells to tell a neighboring group of cells what cellular identity to take on.
Local signaling may also refer to the communication that occurs at the synapse between two neurons. At the
synapse, the axon of the presynaptic neuron releases neurotransmitters which diffuse across the synapse and bind
to receptors on the post-synaptic neuron.
Illustrative Examples of Communication via the Release of Local Regulators
Neurons--The neuron is the basic working unit of the nervous system. Neurons are specialized cells designed to
transmit information to other nerve cells, muscle cells, or gland cells.
Neuron (Nerve cell) structure:
Cell Body or Soma - This portion of the neuron contains the DNA and organelles of the cell. This structure
helps to produce the proteins and other substances needed throughout the rest of the cell.
Dendrites - These structures receive incoming signals from other neurons. Most neurons have several dendrites
that branch out from the soma like tree branches. The dendrites have ligand-gated ion channel receptors that
interact with neurotransmitters released by other neurons.
Axon – The axon transmits the signal to the next neuron or muscle cell. It typically does this by releasing
neurotransmitters which bond to receptors on the next cell in the chain.
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Synaptic Terminal – This term refers to the end of the axon found at a synapse.
Synapse - This is the gap between neurons or between a neuron and an effector cell.
Neurotransmitter – Neurotransmitters are chemical signals that are produced by the neuron that are used to
transmit the signal across the synapse and to the next neuron. Example neurotransmitters include:
Acetylcholine, Dopamine, Serotonin, Nitric Oxide, Epinephrine, and Norepinephrine.
Neurotransmitters are released from the axon terminal of the Presynaptic neuron.
Neurotransmitters are received by the receptors on the dendrites of the Postsynaptic neuron. Once enough
neurotransmitters bind to the receptors, an action potential/nerve impulse is initiated in the post synaptic neuron.
Neuron Structure
The Synapse
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Morphogens
Morphogens are secreted signaling molecules that diffuse from local sources to form concentration gradients,
which specify multiple cell fates during embryonic development. One of the most famous morphogens is the
Sonic Hedgehog protein. Sonic hedgehog is one of three proteins in the mammalian signaling pathway family
called hedgehog, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best
studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such
as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example
of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form
a concentration gradient and has different effects on the cells of the developing embryo depending on its
concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been
implicated in the development of some cancers.
Quorum Sensing in Bacteria
Unicellular prokaryotes, like bacteria, also possess mechanisms for cell to cell communication. One of the most
important examples of a local signaling mechanism in bacteria is quorum sensing. Quorum sensing (QS) is a
bacterial cell–cell communication process that involves the production, release, detection, and response to
extracellular signaling molecules called autoinducers (AIs). AIs accumulate in the environment as the bacterial
population density increases, and bacteria monitor this information to track changes in their cell numbers and
collectively alter gene expression. QS controls genes that direct activities that are only beneficial when performed
by groups of bacteria acting in synchrony. These genes are only activated when the bacterial density in the local
area is high enough for their actions to be beneficial. Processes controlled by QS include bioluminescence,
sporulation, competence, antibiotic production, biofilm formation, and virulence factor secretion.
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Long Distance
Long distance signaling may occur between cells (in the same organism) that are located far apart or
between two different organisms that are separated by large distances.
Hormones – Hormones are chemical messengers that are released directly into the bloodstream from an
endocrine gland located in one part of the body. The hormones travel through the blood to specific cells (target
cells) that have the appropriate receptor for the hormone. The binding of the hormone to the receptor transmits
the message to the target cell. Hormones are typically composed of either proteins or steroids (lipids).
Pheromones - Pheromones are chemicals capable of acting like hormones outside the body of the
secreting individual, to impact the behavior of the receiving individuals. There
are alarm pheromones, food trail pheromones, sex pheromones, and many others that affect behavior or
physiology. Pheromones are used from basic unicellular prokaryotes to
complex multicellular eukaryotes. Pheromones are usually made from steroids (lipids).
Illustrative Examples of Cellular Communication That Occurs Over Long Distances
Blood Glucose Maintenance
When blood glucose levels rise above the set point range, the pancreas releases the hormone insulin.
Insulin travels throughout the body via the bloodstream. It binds to receptors on numerous types of body cells
like those in the liver and muscles. Once insulin attaches to the receptors, the signal transduction pathway that it
initiates ultimately causes the target cells to absorb glucose from the blood and store it within the cell. This
lowers the blood glucose level.
When blood glucose levels drop below the set point range, the pancreas releases the hormone glucagon.
Glucagon travels throughout the body via the bloodstream. It binds to receptors on numerous types of body cells
like those in the liver and muscles. Once glucagon attaches to the receptors, the signal transduction pathway that
it initiates ultimately causes the target cells to breakdown glucose storage molecules like glycogen and to release
the freed glucose into the bloodstream. This ultimately raises the blood glucose level.
The levels of insulin and glucagon in the bloodstream are regulated by a negative feedback loop.
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Steroid Hormones
Other hormones like testosterone and estrogen are steroid (lipid-based) hormones which are capable of passing
through the cell membrane. Once inside the cell, these hormones bind to intracellular receptors.
The hormone/receptor complex enters the nucleus and acts as a transcription factor. This transcription factor causes
the activation of a specific gene or set of genes.
The responses caused by steroid hormones are typically slower than those caused by protein hormones, but the
responses caused by steroid hormones are typically longer in duration.
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Signal Transduction Pathway
Signal Transduction pathways link signal reception with cellular responses. The pathways usually involve a
group of molecules in a cell that work together to control one or more cell functions, such as cell division or cell
death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated
until the last molecule is activated and the cell function is carried out.
Ligand – Ligand is another name for a signaling molecule.
The ligand binds to the receptor protein on the cell membrane (if the ligand is made of protein) or inside the cell
(if the ligand is a steroid/lipid).
The attachment of the ligand to the receptor causes a conformational shape change in the receptor protein that
sets in motion the signal transduction pathway.
Different ligands can initiate different responses. The same ligand can initiate different responses in different
types of cells because these cells contain different signal transduction pathways.
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Three parts to the pathway:
Reception – Reception begins when the signaling molecule binds to the ligand binding domain of
a membrane receptor protein.
The receptors are very specific to a particular signaling molecule. The signal molecule must fit into
the receptor like a substrate fits into the active site of an enzyme. Different cells possess different
receptors and are capable of interacting with different signaling molecules. Most receptors extend
outside the cell membrane (extracellular receptors) because most signaling molecules are composed
of proteins This means that they are too large and charged to enter the cell. After the signal
molecule attaches to the receptor, the intracellular domain of the receptor protein (the part of the
receptor protein that extends through the membrane and into the cytoplasm) undergoes a
conformation change (change in shape). This process helps to move the signal from outside to
inside the cell and initiates the transduction of the signal.
It is important to note that mutations in the genes that code for any of the domains (sections)
of the receptor proteins or in any component/protein of the signaling pathway may affect the
other downstream components of the pathway by altering the subsequent transduction of the
signal.
Chemicals which interfere any component of the signaling pathway may activate or inhibit the
pathway.
Note that steroid/lipid-based hormones bind to receptors located inside the cell (intracellular
receptors).
Transduction -- Since signaling systems need to be responsive to small concentrations of chemical
signals and act quickly, cells often use a multi-step pathway that transmits the signal quickly, while
amplifying the signal to numerous molecules at each step. Steps in the signal transduction pathway
often involve the addition or removal of phosphate groups which results in the activation of
proteins. Enzymes that transfer phosphate groups and energy from ATP to a protein are
called protein kinases. Many of the relay molecules in a signal transduction pathway are protein
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kinases and often act on other protein kinases in the pathway. Often this creates a phosphorylation
cascade, where one enzyme phosphorylates another, which then phosphorylates another protein,
causing a chain reaction. Also important to the phosphorylation cascade are a group of proteins
known as protein phosphatases. Protein phosphatases are enzymes that can rapidly remove
phosphate groups from proteins (dephosphorylation) and thus inactivate protein kinases. Protein
phosphatases are the “off switch” in the signal transduction pathway.
A benefit of transduction is that a small number of ligands (signals) can help to activate a large
number of molecules at the end of the pathway. We can say that transduction often amplifies a
chemical signal along the signal transduction pathway.
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Response – The response is the action the signal was meant to initiate and/or regulate. A signal transduction
pathway regulates one or more cellular activities. Potential responses to cell signals include:
The opening of an ion channel—Example: The opening of ligand gated ion channels on neurons in
response to the binding of neurotransmitters.
The breakdown of a substance in a cell—The breakdown of glycogen in the liver stimulated by the binding
of epinephrine to receptors on the liver cells.
The synthesis of enzymes or proteins (gene expression)—Rising levels of ethylene gas cause the
production and activation of enzymes that cause the ripening of fruits.
The turning on/off of certain genes (gene regulation)—The expression of the SRY gene triggers the
development of the male sexual development pathway.
Hox genes are a group of related genes that specify regions of the body plan of an embryo along the head-tail
axis of animals. Hox genes actually code for transcription factors which cause the expression of genes that
encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct
places of the body. For example, Hox genes in insects specify which appendages form on a segment (e.g.
legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae
that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not
form the actual segments themselves.
An analogy for the Hox genes can be made to the role of a play director that calls which scene the actors
should carry out next. If the play director calls the scenes in the wrong order, the overall play will be
presented in the wrong order. Similarly, mutations in the Hox genes can result in body parts and limbs in the
wrong place along the body. Like a play director, the Hox genes do not act in the play or participate in limb
formation themselves.
Cell Growth/Reproduction—Cytokines are cell signals that regulate gene expression and stimulate cell
replication and division.
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Unit 4 Cell Communication Student Notes Page 14
AP Biology
Cell Communication Part 2
Types of Signal Receptors
G- Protein Linked Receptor
G-Protein-Linked Receptors-- These extracellular receptors are the largest and most diverse group of
receptors found in eukaryotes. G-protein-linked receptors may bind ligands which range from odor
molecules to pheromones to hormones to neurotransmitters.
Once a ligand binds to the G-protein-linked receptor, a GTP molecule is attached to the alpha subunit of the
receptor. The alpha subunit then breaks free (the conformational change) and activates a protein/enzyme
which creates multiple secondary messengers like cAMP. The job of a secondary messenger is to transmit
the signal from just inside the cell membrane throughout the rest of the cytoplasm.
Secondary messengers stimulate the proteins of the signal transduction pathway and the creation of multiple
secondary messengers in response to one ligand. This starts the amplification (spreading of the signal
throughout the cell) of the signal.
A limitation of individual G-protein-linked receptors is that they can only activate one signal transduction
pathway and thus bring about one, specific response.
Receptor Tyrosine Kinases
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Receptor Tyrosine Kinase (RTK)-- These cell surface (extracellular) receptors bind and respond to growth factors
and other locally released proteins that are present at low concentrations. RTKs play important roles in
the regulation of cell growth, differentiation, and survival. Insulin receptors are an example of this category of
extracellular receptors. When signaling molecules bind to RTKs, they cause neighboring RTKs to associate with
each other, forming cross-linked dimers. Cross-linking activates the tyrosine kinase activity in these RTKs
through phosphorylation. Each RTK in the dimer phosphorylates multiple tyrosines on the other RTK. This
process is called cross-phosphorylation.
This allows receptor tyrosine kinases to activate multiple signal transduction pathways at a time and stimulate
multiple cellular responses.
RTKs are often involved with growth/emergency repair processes.
Ligand Gated Ion Channels
Certain cells, commonly called excitable cells, are unique because of their ability to generate electrical signals.
Although several types of excitable cells exist — including neurons, muscle cells, and touch receptor cells — all
of them use ligand-gated ion channel receptors to convert chemical or mechanical messages into electrical
signals.
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Intracellular Receptors
These receptors are mostly for steroids. Since these molecules are lipids, they don’t need receptor
proteins on the cell membrane. They travel into the cell by diffusing across the phospholipid bi-layer.
Steroids such as estrogen and testosterone are able to cross the cell membrane (because of their lipid
nature) and interact with intracellular receptors.
The steroid and receptor complex then enters the nucleus and acts as a gene regulatory protein. These
proteins can stimulate the transcription of specific genes. Essentially, they can “turn on” specific
genes. Because they can enter the cell and stimulate specific genes, steroids can often stimulate
responses that are slower, but more sustained than those caused by protein-based signals that interact
with extracellular receptors.
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Feedback Loops
Homeostasis--a property of an organism or system that helps it maintain its parameters (temperature, blood glucose levels,
blood calcium levels, heart rate, blood pressure, etc..) within a normal (fairly constant) range of values. One of the main
functions of the endocrine system is to help maintain homeostasis.
Feedback loops are mechanisms used by organisms to maintain their internal environments and respond to internal and
external environmental changes.
Negative Feedback Loop—A negative feedback loop occurs in biology when the product of a reaction leads to a decrease in
that reaction. In this way, a negative feedback loop brings a system closer to a target set point of stability or homeostasis.
Negative feedback loops are responsible for the stabilization of a system, and ensure the maintenance of a steady, stable
internal state. The response of the regulating mechanism is opposite to the output of the event. Another way of thinking
about negative feedback loops is that if a system is perturbed/disturbed, negative feedback mechanisms return the system to
its target set point. These mechanisms operate on both the molecular and cellular levels. Examples in the human body
include: Thermoregulation; Maintenance of blood glucose levels; Maintenance of blood calcium levels.
Components of a Negative Feedback Loop
Stimulus—a change in a variable away from the set point range.
Receptor—senses a change in a variable.
Control Center—compares the changes to the set point range. Sends out either nervous or endocrine signals to
effectors which will reverse the change back toward the set point. In many human feedback loops, the control
center is the hypothalamus.
Effector—makes adjustments to the variable.
Response—change in the variable caused by the effector.
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Idealized Negative Feedback Loop
Negative Feedback Loop for Blood Glucose Maintenance
Insulin is normally secreted by the beta cells (a type of islet cell) of the pancreas. The stimulus for insulin secretion is a HIGH
blood glucose...it's as simple as that! Although there is always a low level of insulin secreted by the pancreas, the amount
secreted into the blood increases as the blood glucose rises. Similarly, as blood glucose falls, the amount of insulin secreted by
the pancreatic islets goes down.
As can be seen in the picture below, insulin has an effect on a number of cells, including muscle, red blood cells, and fat
cells. In response to insulin, these cells absorb glucose out of the blood, having the net effect of lowering the high blood
glucose levels into the normal range.
Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin...except in the opposite
direction. If blood glucose is high, then no glucagon is secreted.
When blood glucose goes LOW, however, (such as between meals, and during exercise) more and more glucagon is secreted.
Like insulin, glucagon has an effect on many cells of the body, but most notably the liver.
The effect of glucagon is to make the liver release the glucose it has stored in its cells into the bloodstream, with the net effect
of increasing blood glucose. Glucagon also induces the liver (and some other cells such as muscle) to make glucose out of
building blocks obtained from other nutrients found in the body (eg, protein).
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Positive Feedback Loops
Positive Feedback Loop--A positive feedback loop occurs in nature when the product of a reaction leads
to an increase in that reaction. If we look at a system in homeostasis, a positive feedback loop moves a
system further away from the target of equilibrium. It does this by amplifying the effects of a product or
event and occurs when something needs to happen quickly. Breast milk production and release—The act
of suckling by an infant causes the pituitary gland to release prolactin, which leads to milk production;
more suckling leads to more prolactin release, which in turn leads to more lactation. This is a positive
feedback system as the product (milk) produces more suckling and more hormone. When the child is no
longer breast feeding, the prolactin drops off and milk production goes down.
A baby pushing against the cervix causes the cervix to stretch. The stretching causes nerve impulses to
travel to the brain. This stimulates the release of the hormone oxytocin by the pituitary gland. The
oxytocin binds to receptors on the cells of the uterine wall and stimulates it to contract. This causes the
cervix to stretch even more, which causes the release of more oxytocin, which causes more frequent and
stronger uterine contractions.
A ripening apple releases the hormone known as ethylene gas. This hormone stimulates neighboring
apples to ripen. This causes the release of more ethylene gas which causes even more apples to ripen.
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Positive Feedback Loop for Childbirth
Positive Feedback Loop for Fruit Ripening
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AP Biology
Introduction to the Cell Cycle
ALL cells undergo three basic processes associated with reproduction/division.
• Replication of the DNA within the parent cell. This occurs in what is referred to as the “S phase”.
(Synthesis phase). Each cell must have a complete copy of the DNA. The DNA in each cell is
identical.
• Replication of any items that are in the cytoplasm, such as ribosomes and organelles (only in eukaryotic
cells).
• Division of the cytoplasm and cell membrane. This is referred to as cytokinesis.
Binary Fission (Prokaryotic Fission) in Prokaryotes
This is the process of Reproduction/Replication in prokaryotes (bacteria). Binary Fission is a type of asexual
reproduction. The process does not create any genetic diversity.
DNA replication (S phase) starts at a single “origin of replication” and works around the entire single, circular
chromosome. This results in two identical circular chromosomes in the nucleoid region.
This is followed by the production of a cleavage furrow in the cell membrane (cytokinesis) to produce 2 new
cells, that are referred to as clones.
The cleavage furrow is produced using actin and myosin (protein) microfilaments of the cytoskeleton.
The two resulting cells are called clones because they possess 100% identical DNA strands.
Biologists think that binary fission evolved into Mitosis as the DNA content of cells increased dramatically.
Binary Fission
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Vocabulary Related to Eukaryotic Cell Division
Cell Cycle—The life cycle of the cell. This includes times in which the cell grows and carries out its designated function(s)
and times in which it replicates its DNA and divides. The cell cycle is a highly regulated series of events for the growth
and development of cells. The cell cycle is a highly regulated series of events for the growth and development of cells.
Parent or Mother cell—The original cell that begins to divide.
Daughter cells—The two identical cells that result from the division of the mother cell. These cells are genetically identical
clones.
Genome – The entire genetic material (DNA) for an organism or cell.
In humans, the genome length is about 2 m or 7 ft. per cell.
Chromatin – This term refers to DNA in its loose, non-chromosome, formation. In this state DNA can be replicated and
transcribed.
Chromosomes – This term refers to DNA in its tightly coiled state. Chromosomes are only present in a cell just before
and during the process of cell division.
Somatic cells (“soma” means body) - These are normal body cells.
These are the cells that make up the majority of an organism.
Their chromosomal content is 2n or diploid. This means that these cells have two copies of each type of
chromosome. (They get half “n”from the “mother”; half “n” from the “father”.)
For humans cells, the diploid number is 46 chromosomes = 2n. (n= 23 in the egg; n=23 in the sperm.)
Germ cells- These are the only cells in the human body that are capable of doing meiosis. Meiosis forms four haploid
gametes (sperm or egg cells) from each diploid germ cell.
Meiosis is the process of making haploid sperm or eggs.
Histones
These are the proteins that help DNA coil up “condense” to form chromosomes during cell division.
When DNA is wrapped around these histones, the whole combined structure is referred to as a nucleosome.
The histones also play an important role in gene regulation.
Sister Chromatids--A portion of the whole “duplicated” chromosome.
This term refers to half of a duplicated or bivalent chromosome. Duplicated or bivalent chromosomes look like
an “X”.
The two halves are held together at the centromere , which is a group of proteins in a constricted portion of the
chromosome.
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The “homologous chromosomes” pictured above are bivalent or duplicated. Homologous means that the
two chromosomes are of the same type and control the same traits.
Mitosis vs. Meiosis
Mitosis – This process refers to ordinary cell division. Almost all cells in the body carry out mitosis. After
mitosis and cytokinesis, one mother cell forms two identical daughter cells. Mitosis is a form of cloning. Its
functions include repair of tissue damage, replacement of old/worn out cells, growth, and asexual reproduction (in
some organisms).
.
Meiosis – Meiosis is the process of forming haploid gametes from diploid germ cells. One germ cell forms
four haploid gametes after meiosis. The four gametes are genetically different from each other. Meiosis is an
important source of genetic variation.
AP Biology
Stages of the Cell Cycle/Cell Cycle Regulation
Phases of the Eukaryotic Cell Cycle:
Interphase
Cells spend up to 90% of their existence in Interphase. Interphase is not part of mitosis. It is the time
during the cell division in which the cell carries out ordinary, everyday growth, activity, and/or repair of
the cell.
Interphase consists of three parts:
G1 (Primary or “first” growth)
During this stage ordinary, everyday growth, activity, and/or repair of the cell takes place.
Organelles begin replicating.
The first checkpoint of the cell cycle occurs at the end of G1.
A checkpoint is one of several points in the eukaryotic cell cycle at which the
progression of a cell to the next stage in the cycle can be halted until conditions are
favorable.
The cell will only pass the G1 checkpoint if it is an appropriate size and has adequate
energy reserves. At this point, the cell also checks for DNA damage. A cell that does not
meet all the requirements will not progress to the S phase. The cell can halt the cycle and
attempt to remedy the problematic condition, or the cell can advance into G(inactive)
0
phase and await further signals when conditions improve.
.
S (synthesis)
During S phase, DNA replicates or is synthesized.
In humans, the 46 single chromatid chromosomes are replicated to form 46 bivalent
chromosomes.
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G2 (Secondary or “second” growth)
During G2, the organelles enlarge and are replicated.
The newly synthesized DNA is checked for errors.
The second checkpoint occurs at the end of G2. The Gcheckpoint bars entry into the
2
mitotic phase if certain conditions are not met. As with the Gcheckpoint, cell size and
1
protein reserves are assessed. However, the most important role of the Gcheckpoint is to
2
ensure that all of the chromosomes have been accurately replicated without mistakes or
damage. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is
halted and the cell attempts to either complete DNA replication or repair the damaged
DNA.
Mitosis- Mitosis ensures the transfer of a complete genome from a parent cell to two genetically identical daughter
cells. Mitosis is technically not “cell division”. Mitosis is a form of nuclear division. It is followed by the process of
cytokinesis which divides the cell or cytoplasm.
Mitosis plays an important role in the processes of growth, tissue repair, and asexual reproduction.
Mitosis occurs in the sequential stages of—Prophase, Metaphase, Anaphase, and Telophase. Note that some textbook
authors choose to divide prophase into two phases (prophase and prometaphase).
Prophase
During prophase, the nuclear envelope is broken down and the centrosomes construct the
spindle apparatus.
The chromatin condenses to form “X” shaped bivalent chromosomes. (Two chromatids.)
Centrioles move toward the poles. Note that plant cells don’t have centrioles.
The spindle fibers begin to attach to each chromosome at a point on the chromosome called
the kinetochore (a part of the centromere).
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Metaphase (“meta” means “middle”)
The chromosomes are pulled toward the middle of the cell and line up on the metaphase
plate. (Middle of cell.)
The third checkpoint occurs at the end of metaphase. The M checkpoint occurs near the
end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle
checkpoint because it determines whether all the sister chromatids are correctly attached to
the spindle microtubules. Because the separation of the sister chromatids during anaphase
is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister
chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of
the cell. As the chromosomes’ kinetochores connect with the spindle apparatus, enzymes
are “turned on”. The enzymes are called Anaphase Promoting Complexes. (APC). When
concentration levels of APC reach the checkpoint level, Anaphase begins. The process
described above is sometimes referred to as the kinetochore signal.
Anaphase (“ana” means “separate”)
Each of the bivalent chromosomes are pulled apart and the two chromatids from each
bivalent chromosome (now referred to as a chromosomes) are pulled towards opposite
poles (ends) of the cell.
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The spindle apparatus is broken down as the two sister chromosomes are “walked” toward
the poles by motor proteins which use ATP as an energy source.
Telophase (“telo” means “last”)
A new nuclear envelope is built around each of the two sets of DNA.
The chromosomes begin to decondense back to their chromatin state.
A cleavage furrow begins to form using actin and myosin microfilaments.
Telophase can be thought of as the opposite of prophase.
Cytokinesis (“Cleavage” means “split”) - This is the division of the cytoplasm.
The cytoplasm and cell organelles are separated to produce two genetically identical daughter cells.
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Unit 4 Cell Communication Student Notes Page 27
G0 (Zero growth phase)
The G0 phase is a period in the cell cycle in which cells exist in a quiescent/non-dividing state. G0 phase
is viewed as either an extended G1 phase, where the cell is neither dividing nor preparing to divide, or a
distinct quiescent stage that occurs outside of the cell cycle. G0 is sometimes referred to as a "post-
mitotic" state, since cells in G0 are in a non-dividing phase outside of the cell cycle. Some types of cells,
such as nerve and heart muscle cells, become post-mitotic when they reach maturity (i.e., when they are
terminally differentiated) but continue to perform their main functions for the rest of the organism's life.
These cells will never re-enter the normal cell cycle. Multinucleated muscle cells that do not undergo
cytokinesis are also often considered to be in the G0 stage. On occasion, a distinction in terms is made
between a G0 cell and a 'post-mitotic' cell (e.g., heart muscle cells and neurons), which will never enter
the G1 phase, whereas other G0 cells may. There are cases in which cells in the G0 phase reenter the
normal cell cycle in response to certain environmental cues.
Spindle Apparatus
The spindle apparatus is composed of a network of protein filaments (mostly microtubules).
The construction begins at the centrosome (where the centrioles are) and works toward the chromosomes.
The spindle fibers attach to the kinetochore on the centromere of the replicated chromosomes.
Motor Proteins “walk” the chromosomes/sister chromatids toward the opposite poles (ends) using ATP as a
source of energy.
Non-kinetochore spindles are used to “push” the poles farther apart (to elongate the cell) and to help produce the
cleavage furrow.
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Cell Plate
Centrioles (in animal cells) act as anchorage points for the spindle fibers.
Plant cells DO NOT have centrioles because the cell wall is used as an anchor point for the spindle fibers.
When plant cells divide, a NEW cell wall “Plate” develops, using small segments of cellulose. There is not a
need for a cleavage furrow.
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Regulation “control” of the Cell Cycle.
Regulation is crucial for normal growth and development.
Regulation varies from cell type to cell type.
The most important form of regulation involves protein-based cell signals called Cyclins.
Checkpoints are also important. See the discussion included above for information pertaining to the three
cell cycle checkpoints.
Cyclin Production
The cyclin concentration in a cell increases from S phase until Anaphase.
Cyclins combine with an inactive enzyme known as Cyclin dependent Kinase (CdK) to form an active enzyme
known as Maturation Promoting Factor (MPF). MPF causes the cell to enter mitosis because it phosphorylates the
nuclear lamina and causes the nuclear membrane to begin the process of disintegration.
Cyclins are degraded after Mitosis leaving only CdK behind. Without cyclin, CDK is inactive.
This process essentially resets the “life clock” for the cell.
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Unit 4 Cell Communication Student Notes Page 30
The Cell Cycle and Cancer
Cancer (ABNORMAL cell growth/reproduction)
Cancer “creates”abnormally high Cyclin production within cells.
No checkpoints exist within cancerous cells, so there is no density-dependent inhibition.
Cancer cells are considered “immortal” as long as they have oxygen and nutrients.
Angiogenesis occurs – Angiogenesis is the “creation of new blood vessels” to “feed” the tumor.
Cancer cells have active telomerase enzymes present. A telomere is a region of
repetitive sequences at each end of eukaryotic chromosomes in most eukaryotes. Telomeres protect
the end of the chromosome from DNA damage or from fusion with neighboring chromosomes.
Telomeres get shorter with every cell division/DNA replication. There is evidence that the length of
the telomeres may regulate the life expectancy of a cell. When the telomeres get to a certain length,
the cell is programmed to undergo apoptosis (cell death). Telomerase is an enzyme that lengthens the
telomeres. The enzyme is active in fetuses, but is mostly inactivated after birth. Since cancer cells
have active telomerase enzymes, their telomeres don’t shorten. This means that they never have to go
through apoptosis and are essentially immortal.
Normal cells divide between 1 and 100 times each. This varies from cell type to cell type.
If no telomeres are present, the cell will not be able to continue dividing.
Cancer starts with Transformation of the DNA in a cell. (Transformation of telomerase to the “on”
setting.)
Things that can causes this to occur: weak genetic history, trauma, a viral insert of DNA/RNA and/or
repeated carcinogen exposure.