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AP Biology Unit 4

Cell Signaling

topics 1,2,3, and 4:

cell communication

-critical for the function and survival of cells

-responsible for the growth and development of multicellular organisms

how do cells communicate?

  • direct contact

  • local signaling

  • long distance signaling

direct contact

-communication through cell junctions

-signaling substances and other material dissolved in the cytoplasm can pass freely between adjacent (next to each other) cells.

  • animal cells: gap junctions

  • plant cells: plasmodesmata

    -key to remember the difference: plant and plasmodesmata both start with P

    -an example of direct contact are immune cells

    Gap JunctionPlasmodesmata

Local Regulators

-a secreting cell will release chemical messages (local regulators/ligands) that travel a SHORT distance through the extra cellular fluid

-the chemical messages will cause a response in a target cell

  • paracrine

  • synaptic

-paracrine: secretory cells release local regulators (growth factors) via exocytosis to an adjacent cell

Paracrine

-synaptic: occurs in animal nervous systems, neurons secrete neurotransmitters and diffuse across the synaptic clef-space between the nerve cell and target cell

Synaptic

Long Distance Signaling

-animals and plants use hormones for long distance signaling

-plants: release hormones that travel in plant vascular tissue (xylem and phloem) or through the air to reach target tissues

-animals: use endocrine signaling, specialized cells release hormones into the circulatory system where they reach target cells

example: insulin

-insulin is released by the pancreas into the bloodstream where it circulates through the body and binds to target cells


Cell Signaling

three stages:

  • reception

    -ligand binds to receptor

  • transduction

    -signal is converted

  • response

    -a cell process is altered


stage one: reception

the detection and receiving of a ligand by a receptor in the target cell

receptor: macromolecule that binds to a signal molecule (ligand)

-receptors can be located in either the plasma membrane or intracellular

  • all receptors have an area that interacts with the ligand and an area that transmits a signal to another protein

  • binding between ligand and receptors is highly specific

-when the ligand binds to the receptor, the receptor activates (via a conformational change)

-allows the receptor to interact with other cellular molecules

-initiates transduction signals

Reception

plasma membrane receptors vs intracellular receptors

plasma membrane:

-most common type of receptor

-binds to ligands that are polar, water-soluble, and large

examples:

  • ligand gated ion channels

  • G protein coupled receptors (GPCRs)

intracellular receptors

-found in the cytoplasm or nucleus of target cell

-binds to ligands that can pass through the plasma membrane

examples:

  • hydrophobic molecules

  • steroid and thyroid hormones

  • gasses like nitric oxide

    Intracellular receptor

stage two: transduction

-transduction: a ligand-receptor binding converts the signal into a form that triggers a response in the target cell

-requires a signal transduction pathway

signal transduction pathway:

transforms the binding of a ligand to its receptor into a specific cellular response

-regulates protein activity through phosphorylation by kinase, relaying a signal inside the cell, dephosphorylation by phosphatase, and shutting off the pathways.

dephosphorylation: removal of a phosphate

phosphorylation: addition of a phosphate

kinase: an enzyme that catalyzes phosphorylation

phosphatase: an enzyme that catalyzes dephosphorylation

-during transduction, the signal is amplified

second messengers: small, non protein molecules and ions help relay the message and amplifed the response; cyclic AMP (cAMP) is a common second messenger

Transduction

stage three: response

response: the final molecule in the signaling pathway converts the signal to a response that will alter a cellular process

examples

  • protein that can alter membrane permability

  • enzyme that will change a metabolic process

  • protein that turns genes on or off

Response

signal transduction pathways

-influence how a cell responds to its environment

-they can result in changes in gene expression and cell function

-can alter phenotypes or result in cell death

changes in signal transduction pathways

-mutations to receptor proteins or to any component of the signaling pathway will result in change to the transduction of the signal


important receptors:

-G protein coupled receptors (GPCRs)

-Ion Channels

GPCRs

  • largest category of cell surface receptors

  • important in animal sensory systems

  • binds to a G protein that can bind to GTP (similar to ATP)

  • the GPCR, enzyme, and G protein are inactive until ligand binding to GPCR on the extracellular side

    • ligand binding causes cytoplasmic side to change shape

    • allows for the G protein to bind to GPCR

    • activates the GPCR and G protein

    • GDP becomes GTP

  • part of the activated G protein can then bind to the enzyme

    • activates enzyme

    • amplifies signal and leads to a cellular response


ion channels

ligand gated ion channels

-located:

in the plasma membrane

-important in the:

nervous system

  • receptors that act as a gate for ions

  • when a ligand binds to the receptor, the “gate” opens/closes allowing the diffusion of specific ions

  • initiates a series of events that lead to a cellular response


quorum sensing

-controlled through population density

-quorum sensing could be used to solve antibiotic resistance through pathogency


topic five

homeostasis- the state of relatively stable internal conditions

feedback loops

  • negative

    • reduces the effect of the stimulus

    • the most common feedback

    • sweat, blood sugar, heart rate

  • positive

    • increases the effect of the stimulus

    • child labor, blood clotting, fruit ripening

the difference summarized: negative feedback reduces a stimulus’s effect to maintain homeostasis, while positive feedback amplifies it.

-stimulus: a variable that will cause a response

-receptor/sensor: sensory organs that detect a stimulus (this is sent to the brain)

-effector: muscle or a gland that will respond

-response: changes that either increase or decrease the effect of the stimulus

homeostatic imbalances

-disease: when the body is unable to maintain homeostasis

cell signaling as a means of homeostasis

-in order to maintain homeostasis, the cells in a multicellular organism must be able to communicate, which occurs through the signal transduction pathways


topics six and seven

cell cycle

allows for the reproduction of cells, growth of cells, and tissue repair

the cell cycle is the life of a cell from its formation until it divides

organization of DNA

-dna associates with and wraps around proteins known as histones to form nucleosomes

-strings of nucleosomes form chromatin

-when a cell is not activately dividing, chromatin is in a non-condensed form

-after DNA replication, chromatin condenses to form a chromosome

-since the DNA was replicated, each chromosome has a duplicated copy

-those copies join together to form sister chromatids

  • centromere: the region on each sister chromatid where they are most closely attached (the center)

  • kinetochore: proteins attached to the centromere that link each sister chromatid to the mitotic spindle

genome

  • a genome is all of a cells genetic information (DNA)

prokaryotic: singular, circle DNA

eukaryotic: one or more linear chromosomes

-every eukaryotic has a specific number of chromosomes

-homologous chromsomes: two chromsomes that are the same length, same centromere position, and carry genes with the same characteristic


somatic cells vs gametes

somatic cells:

-body cells

-diploid: two sets of chromosomes

-divide by mitosis

gametes:

-reproductive cells

-haploid: one set of chromosomes

-divide by meiosis


the cell cycle

interphase:

-G1: the cell grows and carries out normal functions

-S “synthesis” phase: DNA replication and chromsome duplication occurs

-G2 phase: final growth and preparation for mitosis

M phase:

mitosis: nucleus divides

  • results in 2 identical diploid daughter cells

cytokenesis: cytoplasm divides


phases of mitosis

  1. prophase

  2. prometaphase

  3. metaphase

  4. anaphase

  5. telophase

phase one: prophase

  • chromatin condenses into visible chromosomes, each with two sister chromatids joined at the centromere

  • the nuclear envelope starts to break down, facilitating the attachment of spindle fibers

  • the mitotic spindle forms and extends from centrosomes that move to opposite poles of the cell, preparing for chromsome movement and alignment

phase two: prometaphase

  • nuclear envelope fragements

  • microtubules enter nuclear area and some attach to kintechores

phase three: metaphase

  • centrosomes are at opposite poles

  • chromosomes line up at the metaphase plate

  • microtubules are attached to each kinetochore

phase four: anaphase

  • sister chromatids seperate and move to opposite ends of the cell due to microtubules shortening

  • cell elongates

phase five: telophase

  • two daughter nuclei form

  • nucleoli reappear

  • chromosomes become less condensed

cytokenesis occurs

animals: a cleavage furrow appears due to a contractile ring of actin filaments

plants: vesicles produced by the golgi travel to the middle of the cell and form a cell plate


review: chromosomes

-cohesins are responsible for holding the sister chromatids together

-DNA is copied by synthesis, which forms sister chromatids because it results in two identical copies of each chromosomes

-gametes are reproductive cells

-somatic cells are anything other than reproductive cells

-eukaryotic cells undergoes mitosis

-a haploid contains one set of chromosomes (haploid number for humans is 23)

-a diploid contains two sets of chromosomes (diploid number for humans is 46)


regulation of the cell cycle

-throughout the cell there are checkpoints

G1 checkpoint:

  • most important

  • checks for cell size, growth factors, and DNA damage

stop/go signals:

-go: completes the whole cell cycle

-stop: cell enters a non dividing state known as the G0 phase

G0:

  • some cells stay in the G0 forever (muscle or nerve cells)

  • some cells can be called back into the cell cycle

G2:

  • checks for the completion of DNA replication and DNA damage

stop/go signals:

-go: cell proceeds to mitosis

-stop: cell cycle crops and the cell will attempt to repair damage

  • if the damage cannot be repaired the cell will undergo apoptosis, which is programed cell death

M (spindle) checkpoint:

  • checks for microtubule attachment to chromosomes at the kinetichores at metaphase

stop/go signals:

-go: cell proceeds to anaphase and completes mitosis

-stop: cell will pause mitosis to allow for spindles to finish attaching to chromosomes


internal cell cycle regulators

regulation of the cell cycle involves an internal control system that consists of:

  • proteins known as cycling (synthesized and degraded at specific stages of the cell cycle)

  • enzymes known as cyclin-dependent kinases (CKDs)

    • concentration remains constant through each phase of the cell cycle

    • active ONLY when its specific cyclin is presented

  • each CDK has a specific regulator effect

    • active CDK complexes phosphorylation target proteins, which help regulate key events in the cell cycle


external cell cycle regulators

growth factors:

  • hormones released by cells that stimulate cell growth

    • signal transduction pathway is initiated

    • CDKs are activated leading to progression through the cell cycle

contact (or density) inhibition:

  • cell surface receptors recognize contact with other cells

    • initiates signal transduction pathway that stops the cell cycle in the G1 phase

anchorage dependence:

  • cells rely on attachement to other cells or the extracellular matrix to divide


cancer: evasion of the cell cycle

normal cells become cancerous through: DNA mutations

-DNA mutation: change in DNA


normal cells vs cancer cells

normal cells:

  • follows checkpoints

  • divide on average 20-50 times in culture

  • go through apoptosis when there are errors

cancer cells:

  • don’t follow checkpoints

  • divide infinitely when in culture

  • considered to be immortal

  • evade apoptosis and continue to divide when there are errors


cancer cells

-uncontrollable growth of cancer cells can lead to a tumor (a mass of tissue formed by abnormal cells)

benign tumor: cells are abnormal, but aren’t cancerous

-the cells are unable to spread elsewhere in the body

malignant tumor: cancerous cells

-cells are able to spread somewhere else in the body

metastasis: cells seperate from the tumor and spread elsewhere in the body (malignant tumor)

C

AP Biology Unit 4

Cell Signaling

topics 1,2,3, and 4:

cell communication

-critical for the function and survival of cells

-responsible for the growth and development of multicellular organisms

how do cells communicate?

  • direct contact

  • local signaling

  • long distance signaling

direct contact

-communication through cell junctions

-signaling substances and other material dissolved in the cytoplasm can pass freely between adjacent (next to each other) cells.

  • animal cells: gap junctions

  • plant cells: plasmodesmata

    -key to remember the difference: plant and plasmodesmata both start with P

    -an example of direct contact are immune cells

    Gap JunctionPlasmodesmata

Local Regulators

-a secreting cell will release chemical messages (local regulators/ligands) that travel a SHORT distance through the extra cellular fluid

-the chemical messages will cause a response in a target cell

  • paracrine

  • synaptic

-paracrine: secretory cells release local regulators (growth factors) via exocytosis to an adjacent cell

Paracrine

-synaptic: occurs in animal nervous systems, neurons secrete neurotransmitters and diffuse across the synaptic clef-space between the nerve cell and target cell

Synaptic

Long Distance Signaling

-animals and plants use hormones for long distance signaling

-plants: release hormones that travel in plant vascular tissue (xylem and phloem) or through the air to reach target tissues

-animals: use endocrine signaling, specialized cells release hormones into the circulatory system where they reach target cells

example: insulin

-insulin is released by the pancreas into the bloodstream where it circulates through the body and binds to target cells


Cell Signaling

three stages:

  • reception

    -ligand binds to receptor

  • transduction

    -signal is converted

  • response

    -a cell process is altered


stage one: reception

the detection and receiving of a ligand by a receptor in the target cell

receptor: macromolecule that binds to a signal molecule (ligand)

-receptors can be located in either the plasma membrane or intracellular

  • all receptors have an area that interacts with the ligand and an area that transmits a signal to another protein

  • binding between ligand and receptors is highly specific

-when the ligand binds to the receptor, the receptor activates (via a conformational change)

-allows the receptor to interact with other cellular molecules

-initiates transduction signals

Reception

plasma membrane receptors vs intracellular receptors

plasma membrane:

-most common type of receptor

-binds to ligands that are polar, water-soluble, and large

examples:

  • ligand gated ion channels

  • G protein coupled receptors (GPCRs)

intracellular receptors

-found in the cytoplasm or nucleus of target cell

-binds to ligands that can pass through the plasma membrane

examples:

  • hydrophobic molecules

  • steroid and thyroid hormones

  • gasses like nitric oxide

    Intracellular receptor

stage two: transduction

-transduction: a ligand-receptor binding converts the signal into a form that triggers a response in the target cell

-requires a signal transduction pathway

signal transduction pathway:

transforms the binding of a ligand to its receptor into a specific cellular response

-regulates protein activity through phosphorylation by kinase, relaying a signal inside the cell, dephosphorylation by phosphatase, and shutting off the pathways.

dephosphorylation: removal of a phosphate

phosphorylation: addition of a phosphate

kinase: an enzyme that catalyzes phosphorylation

phosphatase: an enzyme that catalyzes dephosphorylation

-during transduction, the signal is amplified

second messengers: small, non protein molecules and ions help relay the message and amplifed the response; cyclic AMP (cAMP) is a common second messenger

Transduction

stage three: response

response: the final molecule in the signaling pathway converts the signal to a response that will alter a cellular process

examples

  • protein that can alter membrane permability

  • enzyme that will change a metabolic process

  • protein that turns genes on or off

Response

signal transduction pathways

-influence how a cell responds to its environment

-they can result in changes in gene expression and cell function

-can alter phenotypes or result in cell death

changes in signal transduction pathways

-mutations to receptor proteins or to any component of the signaling pathway will result in change to the transduction of the signal


important receptors:

-G protein coupled receptors (GPCRs)

-Ion Channels

GPCRs

  • largest category of cell surface receptors

  • important in animal sensory systems

  • binds to a G protein that can bind to GTP (similar to ATP)

  • the GPCR, enzyme, and G protein are inactive until ligand binding to GPCR on the extracellular side

    • ligand binding causes cytoplasmic side to change shape

    • allows for the G protein to bind to GPCR

    • activates the GPCR and G protein

    • GDP becomes GTP

  • part of the activated G protein can then bind to the enzyme

    • activates enzyme

    • amplifies signal and leads to a cellular response


ion channels

ligand gated ion channels

-located:

in the plasma membrane

-important in the:

nervous system

  • receptors that act as a gate for ions

  • when a ligand binds to the receptor, the “gate” opens/closes allowing the diffusion of specific ions

  • initiates a series of events that lead to a cellular response


quorum sensing

-controlled through population density

-quorum sensing could be used to solve antibiotic resistance through pathogency


topic five

homeostasis- the state of relatively stable internal conditions

feedback loops

  • negative

    • reduces the effect of the stimulus

    • the most common feedback

    • sweat, blood sugar, heart rate

  • positive

    • increases the effect of the stimulus

    • child labor, blood clotting, fruit ripening

the difference summarized: negative feedback reduces a stimulus’s effect to maintain homeostasis, while positive feedback amplifies it.

-stimulus: a variable that will cause a response

-receptor/sensor: sensory organs that detect a stimulus (this is sent to the brain)

-effector: muscle or a gland that will respond

-response: changes that either increase or decrease the effect of the stimulus

homeostatic imbalances

-disease: when the body is unable to maintain homeostasis

cell signaling as a means of homeostasis

-in order to maintain homeostasis, the cells in a multicellular organism must be able to communicate, which occurs through the signal transduction pathways


topics six and seven

cell cycle

allows for the reproduction of cells, growth of cells, and tissue repair

the cell cycle is the life of a cell from its formation until it divides

organization of DNA

-dna associates with and wraps around proteins known as histones to form nucleosomes

-strings of nucleosomes form chromatin

-when a cell is not activately dividing, chromatin is in a non-condensed form

-after DNA replication, chromatin condenses to form a chromosome

-since the DNA was replicated, each chromosome has a duplicated copy

-those copies join together to form sister chromatids

  • centromere: the region on each sister chromatid where they are most closely attached (the center)

  • kinetochore: proteins attached to the centromere that link each sister chromatid to the mitotic spindle

genome

  • a genome is all of a cells genetic information (DNA)

prokaryotic: singular, circle DNA

eukaryotic: one or more linear chromosomes

-every eukaryotic has a specific number of chromosomes

-homologous chromsomes: two chromsomes that are the same length, same centromere position, and carry genes with the same characteristic


somatic cells vs gametes

somatic cells:

-body cells

-diploid: two sets of chromosomes

-divide by mitosis

gametes:

-reproductive cells

-haploid: one set of chromosomes

-divide by meiosis


the cell cycle

interphase:

-G1: the cell grows and carries out normal functions

-S “synthesis” phase: DNA replication and chromsome duplication occurs

-G2 phase: final growth and preparation for mitosis

M phase:

mitosis: nucleus divides

  • results in 2 identical diploid daughter cells

cytokenesis: cytoplasm divides


phases of mitosis

  1. prophase

  2. prometaphase

  3. metaphase

  4. anaphase

  5. telophase

phase one: prophase

  • chromatin condenses into visible chromosomes, each with two sister chromatids joined at the centromere

  • the nuclear envelope starts to break down, facilitating the attachment of spindle fibers

  • the mitotic spindle forms and extends from centrosomes that move to opposite poles of the cell, preparing for chromsome movement and alignment

phase two: prometaphase

  • nuclear envelope fragements

  • microtubules enter nuclear area and some attach to kintechores

phase three: metaphase

  • centrosomes are at opposite poles

  • chromosomes line up at the metaphase plate

  • microtubules are attached to each kinetochore

phase four: anaphase

  • sister chromatids seperate and move to opposite ends of the cell due to microtubules shortening

  • cell elongates

phase five: telophase

  • two daughter nuclei form

  • nucleoli reappear

  • chromosomes become less condensed

cytokenesis occurs

animals: a cleavage furrow appears due to a contractile ring of actin filaments

plants: vesicles produced by the golgi travel to the middle of the cell and form a cell plate


review: chromosomes

-cohesins are responsible for holding the sister chromatids together

-DNA is copied by synthesis, which forms sister chromatids because it results in two identical copies of each chromosomes

-gametes are reproductive cells

-somatic cells are anything other than reproductive cells

-eukaryotic cells undergoes mitosis

-a haploid contains one set of chromosomes (haploid number for humans is 23)

-a diploid contains two sets of chromosomes (diploid number for humans is 46)


regulation of the cell cycle

-throughout the cell there are checkpoints

G1 checkpoint:

  • most important

  • checks for cell size, growth factors, and DNA damage

stop/go signals:

-go: completes the whole cell cycle

-stop: cell enters a non dividing state known as the G0 phase

G0:

  • some cells stay in the G0 forever (muscle or nerve cells)

  • some cells can be called back into the cell cycle

G2:

  • checks for the completion of DNA replication and DNA damage

stop/go signals:

-go: cell proceeds to mitosis

-stop: cell cycle crops and the cell will attempt to repair damage

  • if the damage cannot be repaired the cell will undergo apoptosis, which is programed cell death

M (spindle) checkpoint:

  • checks for microtubule attachment to chromosomes at the kinetichores at metaphase

stop/go signals:

-go: cell proceeds to anaphase and completes mitosis

-stop: cell will pause mitosis to allow for spindles to finish attaching to chromosomes


internal cell cycle regulators

regulation of the cell cycle involves an internal control system that consists of:

  • proteins known as cycling (synthesized and degraded at specific stages of the cell cycle)

  • enzymes known as cyclin-dependent kinases (CKDs)

    • concentration remains constant through each phase of the cell cycle

    • active ONLY when its specific cyclin is presented

  • each CDK has a specific regulator effect

    • active CDK complexes phosphorylation target proteins, which help regulate key events in the cell cycle


external cell cycle regulators

growth factors:

  • hormones released by cells that stimulate cell growth

    • signal transduction pathway is initiated

    • CDKs are activated leading to progression through the cell cycle

contact (or density) inhibition:

  • cell surface receptors recognize contact with other cells

    • initiates signal transduction pathway that stops the cell cycle in the G1 phase

anchorage dependence:

  • cells rely on attachement to other cells or the extracellular matrix to divide


cancer: evasion of the cell cycle

normal cells become cancerous through: DNA mutations

-DNA mutation: change in DNA


normal cells vs cancer cells

normal cells:

  • follows checkpoints

  • divide on average 20-50 times in culture

  • go through apoptosis when there are errors

cancer cells:

  • don’t follow checkpoints

  • divide infinitely when in culture

  • considered to be immortal

  • evade apoptosis and continue to divide when there are errors


cancer cells

-uncontrollable growth of cancer cells can lead to a tumor (a mass of tissue formed by abnormal cells)

benign tumor: cells are abnormal, but aren’t cancerous

-the cells are unable to spread elsewhere in the body

malignant tumor: cancerous cells

-cells are able to spread somewhere else in the body

metastasis: cells seperate from the tumor and spread elsewhere in the body (malignant tumor)

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