Molecular Biology of the Cell Chapter 15 Part 1

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Principles of cell communication

Extracellular chemical signals

For cells in a multicellular organism to function as an organized group they must be able to recognize, and respond to, what?

1. Being able to regulate the signals emitted,
2. Having the released signal recognized by the correct 'receiving' cell,
3. Having the signal 'interpreted' to generate a change in cell behavior

What three things are necessary for cells in a multicellular organism to be able to recognize and respond to extracellular chemical signals?

External signals

Most cells in a multicellular organism can release and receive what?

Single cells that exist in a community

What kind of cells participate in intracellular communication

1. Controlling population density and coordinating motility
2. Influencing antibiotic production, spore formation and sexual conjugation

Bacteria respond to chemical signals secreted by their neighbors for what two functions?

'Quorum sensing'

The signaling process which controls density, coordinates motility, influences antibiotic production, spore formation and sexual conjugation is called what in bacteria?

Single celled and multicellular organisms

The general molecular organization of a signaling pathway are similar for what organisms?

Cell-cell communication

What kind of communication includes receptor proteins, intracellular signaling proteins, and effector proteins?

Receptor proteins

What proteins are often cell surface proteins (several intracellular receptor proteins exist), and are responsible for recognizing the signaling molecule which leads to receptor activation?

Activated receptors

What kind of receptors undergo a conformational change that transmits the signal to an intracellular signaling protein?

On to another protein, which in turn passes it on to another protein in the pathway

The activated intracellular signaling protein passes the signal where?

A signaling cascade

When a signaling protein passes the signal on to another protein, which in turn passes it on establishes a sequence of intracellular signaling events referred to as what?

The effector proteins

The terminal target of internal signaling are what?

Upon their activation

When are effector proteins are altered in some way?

the original signal

Alteration of effector proteins is necessary for implementing the changes dictated by what?

Metabolism, gene expression, cell shape or cell movement

The end result of activation of intracellular signaling may include changes in what?

A: Extracellular signal molecule
B: Receptor protein
C: Intracellular signaling proteins
D: Effector proteins

Identify the structure/signals of the intracellular signaling pathway

A: Altered metabolism
B: Altered gene expression
C: Altered cell shape or movement

Identify the products produced by intracellular signaling pathway

1. Proteins
2. Peptides
3. Amino acids
4. Nucleotides

Give some examples of signaling molecules that use cell surface receptors

1. Steroid hormones
2. Retinoids
3. Vitamin D
4. Nitric oxide (NO)
5. Carbon monoxide (CO)

Give some examples of signaling molecules that use intracellular receptors

Cell-surface receptors and intracellular receptors

What are two different types of receptors?

Cell-surface receptors

Signals such as proteins, peptides, amino acids, or nucleotides are typically recognized by what?

Pass through the plasma membrane to directly bind to intracellular receptors

Small hydrophobic molecules such as steroid hormones, retinoids, and vitamin D as well as dissolved gases like NO and CO can do what?

Within different compartments of the cell

Intracellular receptors may reside where?

Specific at very low concentrations

Signal molecule binding to a receptor is highly what and occurs at what kind of concentrations?

Exocytosis

Signaling molecules are released by the signaling cell by what process?

Plasma membrane

Some signaling molecules can directly diffuse through the cell's what?

Span the plasma membrane and remain tethered to the signaling cell

Some signaling molecules are transmembrane proteins that do what?

Cell-surface receptor

What type of cellular receptor is this?

Intracellular receptor

What type of cellular receptor is this?

"Contact-dependent signaling"

What kind of signaling is it when the signaling molecule remains bound to the extracellular surface of a signaling cell, direct interaction between the signaling cell and the target cell is required?

Events that occur during development and in the immune response

Contact dependent signaling is important for what signaling events?

"Paracrine signaling"

What kind of signaling happens when the signaling molecule acts on neighboring cells the process (the signaling molecule is released by the signaling cell) ?

Different cell types

Paracrine signaling occurs between the same or different cell types?

"Autocrine signaling"

Signaling between the same cell types is called what?

1. Rapid uptake by neighboring cells
2. Degradation by extracellular proteases,
3. Immobilization by extracellular matrix proteins

What mechanisms are used to prevent signal molecule diffusion?

Synaptic and endocrine signaling

Long distance signaling mechanisms include what?

Axonal signaling in neurons

Give an example of synaptic signaling:

Directly to the target cell

Long axonal extension make direct contact with a target cell such that chemical signals released are delivered where?

Signaling molecules (hormones)

In endocrine signaling, endocrine cells secrete their what into the bloodstream

Long distances

How far are hormones carried to act on target cells (short or long distances)

Diffusion and blood flow to carry the signaling molecule to the target cells

Endocrine signaling therefore depends on what? To carry what molecule? To what cells?

A: Contact-dependent
B: Paracrine
C: Synaptic
D: Endocrine

Identify the intracellular signaling pathways?

Slow

Endocrine signaling depends on blood flow for delivery therefore signal transmission is what (fast or slow)?

Synaptic signaling

What kind of signaling is triggered by an electrical signal and is therefore much faster?

Very low concentrations

For endocrine signaling, secreted hormones are diluted in the bloodstream and therefore must be able to function at what concentrations?

High specificity for a particular hormone

Endocrine signaling requires that the target cell express receptors with what?

Very high concentration

For synaptic signaling, neurons release their signaling molecule at what concentration (low or very high) into the extracellular matrix adjacent to the target cells?

Only a low affinity

Synaptic signaling receptors on target cells require what kind of affinity (low or high) for the signal ligand?

A response in different target cells

Endocrine signaling requires that different endocrine cells secrete different hormones to induce what?

Neuronal cells

In synaptic signaling, what cells can use the same signaling molecule to trigger a response in different cells because the synaptic terminii delivers the signal to target cell?

Endocrine signaling

What kind of signaling is this?

Synaptic signaling

What kind of signaling is this?

The method of delivery and the target cells intracellular response to the extracellular signal

Target cell response time to a molecular signal depends on what

Rapid

For signals that induce a change in target cell protein activity, the intracellular response is what (slow or rapid)?

1. Phosphorylation
2. Changes in a proteins subcellular localization
3. Alterations in protein-protein interactions

Changes in protein activity can be induced by what? (three answers)

The desired target cell response

Rapid intracellular responses to an extracellular signal is seen when changes in cell movement, secretion or metabolism is what?

A slow response

Besides rapid responses, extracellular signaling molecules can also induce what kind of response within the target cell

Gene transcription requiring mRNA processing, mRNA export and then protein synthesis

For these signaling molecules, the target cell response involves changes in what? (three answers)

Delivery method of the signaling molecule [rapid (synaptic signaling) or slow (endocrine signaling)]

The two intracellular response pathways [fast (changes in protein activity) or slow (gene transcription)] are not linked to the what?

Fast (<sec to min)

What is the speed of changes in protein changes in A?

Slow (mins to hours)

What is the speed of changes in protein changes in B?

Gap junctions

Transmission of an intracellular response to neighboring cells occurs by the passage of inorganic ions or small water soluble molecules through water-filled channels that directly link adjacent cells. What are these water-filled channels?

Epithelial cells

Where are gap junctions found?

Homogenize the cytoplasm of one cell with its
neighbor

What is the main function of a gap junction?

Intracellular mediators such as calcium or cyclic AMP

Signaling pathways that result in the production of what can transmit this signal to a neighboring cell via passage through gap junctions?

A sympathetic nerve to respond to a signal and pass that intracellular response to an adjacent cell that is not innervated

Cell-cell communication mechanism using gap junctions allows one cell innervated by what? That respond to what? Pass the reponse where? which is not what?

A coordinated manner

Using gap junctions allow cells can respond to extracellular signals in what kind of manner even if not all target cells have bound the signaling molecule?

Gap junction

What is this structure?

Hundreds of different signal molecules

A cell in a multicellular organism is exposed to what?

A target cell response

A cell in a multicellular organism is exposed to hundreds of different signal molecules. It is the combinations of these different signals that induce what?

Different receptors on different target cells

Differential responses are accomplished by the expression of what?

Cell survival, growth, division, differentiation and cell death

Signal molecules work together to regulate what basic functions of the cell?

A: Survive
B: Divide
C: Differentiate
D: Die

Multiple extracellular signals illicit what kind of cellular responses?

Different combinations of extracellulular signal molecules

Cells have different receptors that allows them to respond to what?

Different target cell responses

Different cell types can respond to the same signal to induce what?

Decreased cell contraction,

When the signal molecule acetylcholine is bound to its receptor on a heart muscle, what are the results?

Muscle contraction

When the signal molecule acetylcholine is bound to its receptor on skeletal muscle cells it induces what?

Secretion

When the signal molecule acetylcholine is bound to cell surface receptors on slaivary gland cells, it results in what?

1. Differences in receptors (heart muscle and skeletal muscle cells)
2. Differences in the intracellular signaling pathway activated (heart muscle and salivary gland cells)

The differences in target cell response when different receptors are bound to acetylcholine may be due to what? (2 answers)

B: Decreased rate and force of contraction
C: Muscle contraction
D: Secretion

What are the responses for the heart muscle (B), skeletal muscle cell (C) and salivary gland cell when their receptors are bound by acetylcholine?

The extracellular concentration of the signaling molecule

The same type of target cell can differ in their intracellular response to the same extracellular signal based on what?

The induction of different sets of genes during development

The same type of target cell can differ in their intracellular response to the same extracellular signal based on the extracellular concentration
of the signaling molecule.This differential response is important for what?

Extracellular developmental signals

What are "morphogens"?

The number of signal-receptor complexes activated

The differential response to morphogen concentration is linked to what?

Target cells closest to the source of morphogen have more activated
receptors than target cells furthest from the morphogen source

Which cells have more activated receptors - (the target cells closest to the source of morphogen or the targets furthest away from the source)?

The amount of gene regulatory proteins activated, and in turn, the pattern of gene
expression between cells found along the morphogen gradient will differ

Differences in receptor activation leads to differences in the what?

Transmembrane proteins found in the plasma membrane of target cells

The most familiar signaling receptors are what?

The cytosol

Some signal molecules activate intracellular receptors found where in the target cells?

Nitric Oxide (the gas)

Give an example of a signal molecule that can pass through the target cell's membrane for intracellular receptor binding?

Induces smooth muscle relaxation

What does NO do?

A multistep signaling cascade

This pathway includes acetylcholine release by an
activated neuronal cell as the primary signal molecule triggering an intracellular response in the endothelial cells that line the interior of a blood vessel. What kind of pathway is it?

The adjacent smooth muscle cells

This target cell then becomes the signal cell which releases a signal molecule for the activation of the next target cell in the pathway, what are they?

NO synthase (NOS)

An activated nerve terminal releases acetylcholine, it binds to the receptor on the underlying endothelial cell activating what?

Arginine

Using what as a substrate NOS generates the gas NO?

The cytosol of the smooth muscle cells

NO diffuses out of the endothelial cell and enters what?

Cyclic GMP

In the cytosol, NO binds to its receptor, soluble guanylyl cyclase triggering the enzymatic
conversion of GTP to what?

Muscle relaxation

cGMP then triggers downstream signaling leading to what?

Cytosolic phosphodiesterases

cGMP is rapidly degraded by what?

The nuclear receptor superfamily (transcription factors)

What is a large family of cytosolic proteins that bind to membrane permeable signals such as steriod hormones, thyroid hormone, retinoids and vitamin D?

1. Lose their bound inhibitory proteins
2. Undergo a change in conformation promoting coactivator
3. Protein binding
4. Trigger a change in target gene transcription

With ligand binding these receptor proteins do what? (4 answers)

Translocation into the nucleus for DNA binding

For some cytosolic localized nuclear receptor family members, ligand binding results in their movement where? For what purpose?

DNA transcription

For other receptor proteins ligand binding prevents what from happening to the DNA?

Both intracellular receptors for signal molecule binding and effectors for the
signal

In all cases, nuclear receptor superfamily members act as what? Give two functions

Only half have identified ligands

Of the 48 different nuclear receptor family members identified in the human genome; how many have identified ligands?

'Orphan' nuclear receptors

What are nuclear receptors with unknown ligands?

Inactive receptor

Is this an active receptor or an inactive receptor?

Active receptor

Is this an active receptor or an inactive receptor?

The primary response

For nuclear receptor proteins that activate gene transcription upon ligand binding, the genes that are directly activated constitute what?

A secondary-response

The primary response proteins can then act to activate the transcription of a second set of genes generating a delayed response to the signal molecule which is referred to as a what?

Negative regulatory loop to limit the response of the initial signal

The primary response gene products can turn off the primary-response genes, acting as a what? To limit what?

A combination of transcription factors which are cell type specific

Many cells express the same set of nuclear receptors however the cellular response they induce will vary from cell type to cell type as gene transcription is regulated by what?

Primary response

What type of response is this (primary or secondary)?

Secondary response

What type of response is this (primary or secondary)?

Signal transduction

What is the process by which cell surface receptor proteins convert extracellular
signals into an intracellular one.

1. Ion channel coupled receptors
2. G-protein coupled receptors
3. Enzyme couple receptors

What are the three general classes of cell surface receptors?

Ion channel coupled receptor

What type of receptor is this?
1. It consists of multipass transmembrane proteins
2. It is opened or closed by the binding of neurotransmitters triggering ion permeability across the plasma membrane
3. It is involved in the synaptic signaling between nerve cells and target cells (muscle or nerve cells)

G protein coupled receptor

What type of receptor is this?
1. It consists of multipass transmembrane proteins
2. It is responsible for the indirect activation of a plasma membrane bound enzyme or ion channel via the activation of an intermediary heterotrimeric GTP binding protein complex
3. Activation leads to changes in the concentration of small intracellular mediates or plasma membrane permeability

Enzyme coupled receptors

What type of receptor is this?
1. It is often single pass transmembrane proteins
2. It functions directly as enzymes (left panel in C) or associates with enzymes that they activate
(right panel in C)
3. Signal molecule binding to the extracellular domain of the protein triggers dimerization
resulting in protein kinase activation which is responsible for phosphorylating specific sets of
proteins in the target cell that they activate

G- Protein

What kind of coupled receptor is this?

Enzyme

What kind of coupled receptor is this?

Ion channel

What kind of coupled receptor is this?

G-protein-coupled or enzyme-coupled receptors

Activation of what two coupled receptors is converted into an intracellular signaling cascade that results in a change in cell behavior?

Secondary messenger

The initial extracellular signal is referred to as the 'first messenger' while the small intracellular signaling molecules generated in response to receptor activation are called what?

To spread the signal to distal portions of the cell

What is the function of the secondary messengers?

Cyclic AMP, calcium, and diacylglycerol

What are some examples of second messengers?

Transduce the original signal throughout the cell

Second messengers bind to larger signaling proteins altering their conformation or activity to do what throughout the cell?

1. Relay
2. Scaffold
3. Convert
4. Amplify
5. Integrate
6. Anchor
7. Modulate

Larger intracellular proteins can have a number of different functions within the cell; Give 7 examples:

Phosphorylation or GTP binding

Transmission of an intracellular signal by the proteins in a signaling pathway is typically carried out by one of two mechanisms: what are they?

Switches

For phosphorylation and GTP binding, the signaling proteins behave as simple molecular what?

Between the off and on forms

What two form do the proteins switch when they receive the get the proper signal?

Protein kinases

(Phosphorylation) The addition of a phosphate group is mediated by what?

Protein phosphatases

(Phosphorylation) What are responsible for removing phosphate groups?

Phosphorylation cascades

(Phosphorylation) Signaling pathways that are mediated by phosphorylation are comprised of multiple protein kinases organized into what?

Relay

One protein kinase is activated by phosphorylation, which in turn phosphorylates the next protein kinase in the pathway leading to its activation. This second kinase then phosphorylates the next kinase protein in the pathway. What type of pathway is it?

Often: serine or threonine; Less often: tyrosine

Often protein kinases phosphorylate proteins on what type of residues and less often on what?

Monmeric GTP binding proteins

What kind of binding proteins are GTPases that are regulated by the state of the guanine nucleotide bound?

The transduction of the signal

When bound to GTP, the binding protein is active promoting what?

Its inactivation and termination of the signal

The intrinsic GTPases activity of the protein converts the GTP to GDP leading to what?

GEFs and GAPs

What two additional proteins are responsible for regulating GTP binding proteins?

GEFs

What are guanine nucleotide exchange factors which function to activate GTPases by promoting the release of GDP for GTP leading to its activation?

GAPs

What are GTPase activating proteins that promote the hydrolysis of the bound GTP leading to the shutting off of the signal?

A: Signaling by phosphorylation
B: Signaling by GTP-binding

Identify the molecular switches (A and B)

The activation of two intracellular pathways that converge at protein Y.

Signal molecule binding to two different receptors results in the activation of what?

The propagation of downstream signaling.

It is the phosphorylation at two different sites on protein Y that
results in what?

Complex biological responses (cell survival, growth and proliferation)

Often it is the combination of two extracellular signals that is required to trigger what? Give some examples!

These two pathways converge at a single protein

Signal molecule binding to two different receptors results in the activation of two intracellular pathways. What happens next?

Coincidence detector

Phosphorylation of a converged protein at two different sites is required for the propagation of downstream signaling
This protein is called a "what"?

When both extracellular signals are present simultaneously

When is the only time that coincidence detector is activated?

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