Cells most often communicate with each other via chemical signals

• For example, the yeast, Saccharomyces cerevisiae, have two mating types, a and α

Cells of different mating types locate each other via secreted factors specific to each type

cells communicate with one another through direct contact with other cells

• cells of multicellular organisms often maintain physical contact with other cells or make physical contact with other cells during certain activities

• some unicellular organisms live in colonies and are in physical contact with other organisms in that colony

• cells can send chemical signals directly to adjacent cells

• cell membrane and cell wall modifications allow for communication to occur between adjacent cells

  • plant cells have plasmodesma

  • animal cells have gap junctions

cells can communicate with one another over short or long distance

• cells use chemical signals to communicate over short and long distances

• the cell receiving the signal is referred to as the target cell

• short-distance communication

  • cell sends out local regulators (signals)

  • target cell is within a short-distance of the signal (local signaling)

  • often used to communicate with cells of the same type

• long-distance communication

  • target cell is not in the same area as the cell emitting the signal

  • signal travels a long distance to reach target cell

  • often used to signal cells of another type

A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

Cells in a multicellular organism communicate by chemical messengers

• Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells

In local signaling, animal cells may communicate by direct contact, or cell-cell recognition

• In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances

• In long-distance signaling, plants and animals use chemicals called hormones

• The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal

Earl Sutherland first discovered signal transduction by studying the effects of epinephrine on cells

• Epinephrine is known as the fight-or-flight hormone

signal transduction pathways link signal reception with cellular responses

Sutherland identified three stages of signal transduction:

1. Reception - detection of a signal molecule coming from outside the cell

2. Transduction - convert signal to a form that can bring about a cell response

3. Response - specific cellular response to the signal molecule

Reception occurs when a signal molecule, or ligand, binds a receptor protein, altering the receptor’s shape

Ligands are highly specific to particular receptors

Receptors are either on the cell surface (membrane receptors) or inside of the cell (cytosolic or intracellular receptors)

• Membrane receptors have polar ligands, while cytosolic receptors have nonpolar ligands

A G-proteincoupled receptor (GPCR) is an example of a membrane receptor

The ligand binds the GPCR extracellular domain, slightly altering the receptor’s shape

1. G-protein is activated by the GPCR and released, as it displaces its GDP with a GTP molecule

   • The active G-protein may begin transduction

   • One GPCR can activate dozens of G-proteins

2. G-protein dephosphorylates its own GTP, forming GDP and  inactivating itself

3. When ligand concentrations drop, the ligand dissociates from the receptor, deactivating the GPCR

Intracellular receptor proteins are found in the cytosol or nucleus of target cells

Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

Examples of hydrophobic messengers are the steroid and thyroid hormones of animals

A ligand-gated ion channel receptor acts as a gate when the receptor changes shape

When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na⁺ or Ca²⁺, through a channel in the receptor

The conformational change in the receptor precipitates a step-wise molecular relay in the cell, indirectly causing a change in the cellular part performing the response

• Multistep pathways can 

  • Amplify a signal: A few molecules can produce a large cellular response

  • Provide more opportunities for coordination and regulation of the cellular response

In many pathways, the signal is transmitted by a cascade of protein phosphorylations

many signal transduction pathways include protein modification and phosphorylation cascades

• regulate protein synthesis by turning on/off genes in nucleus

• regulate activity of proteins in cytoplasm

• cascades of molecular interactions relay signals from receptors to target molecules

• phosphorylation cascade: enhance and amplify signal

Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

The molecules that relay a signal from receptor to response are mostly proteins

• Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated

• At each step, the signal is transduced into a different form, usually a shape change in a protein

signaling begins with the recognition of a chemical messenger - a ligand - by a receptor protein in a target cell

• the ligand-binding domain of a receptor recognizes a specific chemical messenger, which can be a peptide, a small chemical, or a protein, in a specific one-to-one relationship

• g protein-coupled receptors are an example of a receptor protein in eukaryotes

The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger”

• signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, resulting in the appropriate responses by the cell, which could include cell growth, secretion of molecules, or gene expression

  • after the ligand binds, the intracellular domain of a receptor protein changes shape, initiating transduction of the signal

  • binding of ligand-to-ligand channels can cause the channel to open or close

• Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion (molecules that relay and amplify the intracellular signal)

• Second messengers participate in pathways initiated by GPCRs

Cyclic AMP is a common second messenger

A cell’s response occurs when cell signaling leads to regulation of transcription or cytoplasmic activities

A cell’s response can be fine-tuned in the following ways:

• Amplifying the signal (and thus the response)

• Specificity of the response

• Overall efficiency of response, enhanced by scaffolding proteins

• Termination of the signal

signal transduction pathways influence how the cell responds to its environment

• the environment is not static, and organisms need to regulate pathways to respond to changes in the environment

• the ability to respond to stimuli is a characteristic of life and necessary for survival

• 

signal transduction may result in changes in gene expression and cell function

• signaling pathways can target gene expression and alter the amount and/or type of a particular protein produced in a cell

  • changes in protein type and/or amount can result in a phenotype change

Signal transduction can alter phenotype or cause apoptosis

• An example of signal transduction altering phenotype is observed in Y-chromosomalSRY gene activation

Phenotype is manifest in an organism’s appearance

Apoptosis is programmed cell death and occurs during embryonic and fetal development or if a cell is damaged

• Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells

Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

• Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis

Apoptosis can be triggered by

• An extracellular death-signaling ligand 

  • can be the response of a signal transduction

• DNA damage in the nucleus

• Protein misfolding in the endoplasmic reticulum

Alterations to any component of a signal transduction pathway will affect response

Alterations can include mutation or chemical interactions

• Altering any domain in the receptor can affect transduction

• Ras, a proto-oncogene, can cause cancer if mutated

changes in signal transduction pathways can alter cellular response

• mutations in any domain of the receptor protein or in any component of the signaling pathway may effect the downstream components by altering the subsequent transduction of the signal

  • changes in protein structure can result in change in function

  • one disruption in a pathway can affect the downstream reactions

  • 

• chemicals that interfere with any component of the signaling pathway may activate or inhibit the pathway

  • 

Organisms must respond to environmental change in order to maintain homeostasis

• Homeostasis is the constant set of internal conditions of an organism

  • the maintenance of a stable internal environment

• organisms use feedback mechanisms to maintain their internal environments and respond to environmental changes (both internal and external)

• feedback mechanisms are processes used to maintain homeostasis by increasing or decreasing a cellular response to an event

If a stimulus causes an organism’s to migrate away from its homeostatic level, negative feedback mechanisms will restore homeostasis

• “More gets you less”

• negative feedback mechanisms maintain homeostasis for a particular cell condition

  • negative feedback mechanisms maintain homeostasis for a particular condition by regulating physiological processes

  • if a system is disrupted, negative feedback mechanisms return the system back to its target set point

  • these processes operate at the molecular and cellular levels

Rarely, a stimulus causes an organism’s to migrate away from its homeostatic level, and the organism will amplify its response using positive feedback

• “More gets you more”

• positive feedback mechanisms amplify responses and processes in biological organisms

  • the variable initiating the response is moved farther away from the initial set point, disrupting homeostasis

  • amplification occurs when the stimulus is further activated, which, in turn, initiates an additional response that produces the system change

Cell cycle is the life of a cell from formation to its own division (a highly regulated series of events for the growth and reproduction of cells)

• the cell cycle consists of two highly regulated processes

  • interphase

    • growth and preparation

    • interphase involves 3 sequential stages

      • G1 - cell growth

      • S - copies of DNA are made

      • G2 - the cytoplasmic components are doubled in preparation for division

  • m-phase

    • mitosis - division of the nucleus

    • cytokinesis - division of the cytoplasm

  • in eukaryotes, cells transfer genetic information via a highly regulated process

    • mitosis…

      • plays a role in cell growth, tissue repair, and asexual reproduction

      • ensures the transfer of a complete genome from a parent cell to two genetically identical daughter cells

      • alternates with interphase in the cell cycle

      • occurs in a sequential series of steps

        • prophase

        • metaphase

        • anaphase

        • telophase

      • is followed by cytokinesis

        • cytokinesis ensures equal distribution of cytoplasm to both daughter cells

    • cells can enter G0 where cell division no longer occurs, a cell can reenter division with appropriate signals

    • nondividing cells may exit the cell cycle or be held at a particular stage

Cell division is an important component of cell cycle

• In unicellular organisms, division of one cell reproduces the entire organism

• Multicellular organisms depend on cell division for embryonic development, growth and repair

For cells capable of division, the genome must be replicated to ensure the next generation of cells receives the entire complement of DNA

• All the DNA in a cell constitutes the cell’s genome

• A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells)

DNA molecules in a cell are packaged into chromosomes

• Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division

• Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus

Somatic cells (non-reproductive cells) have two sets of chromosomes and are diploid (2n)

Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells and are haploid (n)

In preparation for cell division, DNA is replicated and the chromosomes condense

Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), which separate during cell division

The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached

• During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei

Once separate, the chromatids are called chromosomes

Eukaryotic cell division consists of

• Mitosis, the division of the genetic material in the nucleus

  • a process that ensures the transfer of a complete genome from a parent cell to daughter cells

    • daughter cells carry genomes identical to the parent cell genome

• Cytokinesis, the division of the cytoplasm

The cell cycle consists of

• Mitotic (M) phase: mitosis and cytokinesis

• Interphase: cell growth and copying of chromosomes in preparation for cell division)Interphase (about 90% of the cell cycle) can be divided into subphases

  • G₁ phase (“first gap”)

  • S phase (“synthesis”)

  • G₂ phase (“second gap”)

• The cell grows during all three phases, but chromosomes are duplicated only during the S phase

Mitosis is conventionally divided into five phases

• Prophase

  • nuclear envelope begins to disappear

  • DNA coils into visible chromosomes

  • fibers begin to move double chromosomes toward the center of the cell

• Prometaphase

  • fibers begin to move double chromosomes toward the center of the cell (sometime considered its own phase, sometimes grouped with prophase)

• Metaphase

  • fibers align double chromosomes across the center of the cell

• Anaphase

  • fibers separate double chromosomes into single chromosomes (chromatids)

  • chromosomes separate at the centromere

  • single chromosomes (chromatids) migrate to opposite sides of the cell

• Telophase

  • nuclear envelope reappears and establishes two separate nuclei

  • each nucleus contains a complete genome

  • chromosomes will begin to uncoil

Cytokinesis overlaps the latter stages of mitosis

• cytokinesis will separate the cell into two daughter cells, each containing identical genomes

The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock

• The cell cycle control system is regulated by both internal and external controls

The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

• For many cells, the G₁ checkpoint seems to be the most important 

• If a cell receives a go-ahead signal at the G₁ checkpoint, it will usually complete the S, G₂, and M phases and divide

If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G₀ phase

internal controls or checkpoints regulate progression through the cycle

• G1 checkpoint

  • at the end of G1 phase

  • cell size check

  • nutrient check

  • growth factor check

  • DNA damage check

• G2 checkpoint

  • at the end of G2

  • DNA replication check

  • DNA damage check

• m-spindle checkpoint

  • fiber attachment to chromosome check

Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)

interactions between cyclins and cyclin-dependent kinases control the cell cycle

• cyclins

  • a group of related proteins associated with specific phases of the cell cycle

  • different cyclins are involved in different stages of the cell cycle

  • concentrations can fluctuate depending on cell activity

    • produced to promote cell cycle progression

    • degraded to inhibit cell cycle progression

  • used to activate cyclin-dependent kinases (CDKs)

    • cyclins are specific to the CDK they activate

• cyclin-dependent kinases (CDKs)

  • group of enzymes involved in cell regulation

  • requires cyclin binding for activation

  • phosphorylate substrates, promotes certain cell cycle activities

• Cdks activity fluctuates during the cell cycle because it is controlled by cyclins, so named because their concentrations vary with the cell cycle

• MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G₂ checkpoint into the M phase

Cell cycle can be influenced by external factors

• Growth factors are ligands that initiate cell division

• Anchorage dependence typically requires cells to be bound to a substratum in order to divide

Density-dependent inhibition causes cells to cease dividing once they fill a space

Cancer cells do not respond normally to the body’s control mechanisms

cancer is the result of an unregulated cell cycle with uncontrolled cell division (if there is a change in the DNA in a region coding for one of the proteins needed to regulate the cell cycle, the cell cycle could go unregulated)

• Cancer cells may not need growth factors to grow and divide

  • They may make their own growth factor

  • They may convey a growth factor’s signal without the presence of the growth factor

  • They may have an abnormal cell cycle control system

• Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue

• If abnormal cells remain only at the original site, the lump is called a benign tumor

• Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors