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Eukaryotic Cell Biology > Chapter 15 > Flashcards

Chapter 15 Flashcards

1
Q

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

A

Extracellular chemical signals

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2
Q

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

A
  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
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3
Q

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

A

External signals

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4
Q

What kind of cells participate in intracellular communication

A

Single cells that exist in a community

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5
Q

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

A
  1. Controlling population density and coordinating motility 2. Influencing antibiotic production, spore formation and sexual conjugation
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6
Q

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

A

‘Quorum sensing’

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7
Q

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

A

Single celled and multicellular organisms

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8
Q

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

A

Cell-cell communication

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9
Q

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?

A

Receptor proteins

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10
Q

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

A

Activated receptors

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11
Q

The activated intracellular signaling protein passes the signal where?

A

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

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12
Q

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?

A

A signaling cascade

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13
Q

The terminal target of internal signaling are what?

A

The effector proteins

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14
Q

When are effector proteins are altered in some way?

A

Upon their activation

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15
Q

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

A

the original signal

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16
Q

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

A

Metabolism, gene expression, cell shape or cell movement

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17
Q

Identify the structure/signals of the intracellular signaling pathway

A

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

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18
Q

Identify the products produced by intracellular signaling pathway

A

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

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19
Q

Give some examples of signaling molecules that use cell surface receptors

A
  1. Proteins 2. Peptides 3. Amino acids 4. Nucleotides
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20
Q

Give some examples of signaling molecules that use intracellular receptors

A
  1. Steroid hormones 2. Retinoids 3. Vitamin D 4. Nitric oxide (NO) 5. Carbon monoxide (CO)
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21
Q

What are two different types of receptors?

A

Cell-surface receptors and intracellular receptors

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22
Q

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

A

Cell-surface receptors

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23
Q

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

A

Pass through the plasma membrane to directly bind to intracellular receptors

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24
Q

Intracellular receptors may reside where?

A

Within different compartments of the cell

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25
Q

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

A

Specific at very low concentrations

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26
Q

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

A

Exocytosis

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27
Q

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

A

Plasma membrane

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28
Q

Some signaling molecules are transmembrane proteins that do what?

A

Span the plasma membrane and remain tethered to the signaling cell

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29
Q

What type of cellular receptor is this?

A

Cell-surface receptor

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30
Q

What type of cellular receptor is this?

A

Intracellular receptor

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31
Q

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?

A

Contact-dependent signaling

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32
Q

Contact dependent signaling is important for what signaling events?

A

Events that occur during development and in the immune response

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33
Q

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

A

Paracrine signaling

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34
Q

Paracrine signaling occurs between the same or different cell types?

A

Different cell types

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35
Q

Signaling between the same cell types is called what?

A

Autocrine signaling

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36
Q

What mechanisms are used to prevent signal molecule diffusion?

A
  1. Rapid uptake by neighboring cells 2. Degradation by extracellular proteases, 3. Immobilization by extracellular matrix proteins
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37
Q

Long distance signaling mechanisms include what?

A

Synaptic and endocrine signaling

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38
Q

Give an example of synaptic signaling:

A

Axonal signaling in neurons

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39
Q

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

A

Directly to the target cell

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40
Q

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

A

Signaling molecules (hormones)

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41
Q

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

A

Long distances

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42
Q

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

A

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

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43
Q

Identify the intracellular signaling pathways?

A

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

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44
Q

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

A

Slow

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45
Q

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

A

Synaptic signaling

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46
Q

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

A

Very low concentrations

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47
Q

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

A

High specificity for a particular hormone

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48
Q

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

A

Very high concentration

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49
Q

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

A

Only a low affinity

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50
Q

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

A

A response in different target cells

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51
Q

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?

A

Neuronal cells

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52
Q

What kind of signaling is this?

A

Endocrine signaling

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53
Q

What kind of signaling is this?

A

Synaptic signaling

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54
Q

Target cell response time to a molecular signal depends on what

A

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

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55
Q

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

A

Rapid

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56
Q

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

A
  1. Phosphorylation 2. Changes in a proteins subcellular localization 3. Alterations in protein-protein interactions
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57
Q

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

A

The desired target cell response

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58
Q

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

A

A slow response

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59
Q

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

A

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

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60
Q

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

A

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

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61
Q

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

A

Fast (

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62
Q

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

A

Slow (mins to hours)

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63
Q

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?

A

Gap junctions

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64
Q

Where are gap junctions found?

A

Epithelial cells

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65
Q

What is the main function of a gap junction?

A

Homogenize the cytoplasm of one cell with its neighbor

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66
Q

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

A

Intracellular mediators such as calcium or cyclic AMP

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67
Q

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

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

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68
Q

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?

A

A coordinated manner

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69
Q

What is this structure?

A

Gap junction

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70
Q

A cell in a multicellular organism is exposed to what?

A

Hundreds of different signal molecules

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71
Q

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?

A

A target cell response

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72
Q

Differential responses are accomplished by the expression of what?

A

Different receptors on different target cells

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73
Q

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

A

Cell survival, growth, division, differentiation and cell death

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74
Q

Multiple extracellular signals illicit what kind of cellular responses?

A

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

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75
Q

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

A

Different combinations of extracellulular signal molecules

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76
Q

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

A

Different target cell responses

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77
Q

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

A

Decreased cell contraction,

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78
Q

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

A

Muscle contraction

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79
Q

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

A

Secretion

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80
Q

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

A
  1. Differences in receptors (heart muscle and skeletal muscle cells) 2. Differences in the intracellular signaling pathway activated (heart muscle and salivary gland cells)
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81
Q

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

A

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

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82
Q

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

A

The extracellular concentration of the signaling molecule

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83
Q

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?

A

The induction of different sets of genes during development

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84
Q

What are “morphogens”?

A

Extracellular developmental signals

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85
Q

The differential response to morphogen concentration is linked to what?

A

The number of signal-receptor complexes activated

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86
Q

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

A

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

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87
Q

Differences in receptor activation leads to differences in the what?

A

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

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88
Q

The most familiar signaling receptors are what?

A

Transmembrane proteins found in the plasma membrane of target cells

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89
Q

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

A

The cytosol

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90
Q

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

A

Nitric Oxide (the gas)

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91
Q

What does NO do?

A

Induces smooth muscle relaxation

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92
Q

This pathway includes acetylcholine release by an

A

A multistep signaling cascade

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93
Q

http://o.quizlet.com/FFyv8LmA2bayzHpxqXzd9g.png

A

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?

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94
Q

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?

A

The adjacent smooth muscle cells

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95
Q

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

A

NO synthase (NOS)

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96
Q

Using what as a substrate NOS generates the gas NO?

A

Arginine

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97
Q

NO diffuses out of the endothelial cell and enters what?

A

The cytosol of the smooth muscle cells

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98
Q

In the cytosol, NO binds to its receptor, soluble guanylyl cyclase triggering the enzymatic

A

Cyclic GMP

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99
Q

http://o.quizlet.com/uAJm-7kK3PTW88OhD-8TuQ.png

A

conversion of GTP to what?

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100
Q

cGMP then triggers downstream signaling leading to what?

A

Muscle relaxation

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101
Q

cGMP is rapidly degraded by what?

A

Cytosolic phosphodiesterases

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102
Q

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

A

The nuclear receptor superfamily (transcription factors)

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103
Q

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

A
  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
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104
Q

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

A

Translocation into the nucleus for DNA binding

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105
Q

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

A

DNA transcription

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106
Q

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

A

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

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107
Q

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

A

Only half have identified ligands

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108
Q

What are nuclear receptors with unknown ligands?

A

‘Orphan’ nuclear receptors

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109
Q

Is this an active receptor or an inactive receptor?

A

Inactive receptor

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110
Q

Is this an active receptor or an inactive receptor?

A

Active receptor

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111
Q

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

A

The primary response

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112
Q

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?

A

A secondary-response

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113
Q

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

A

Negative regulatory loop to limit the response of the initial signal

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114
Q

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?

A

A combination of transcription factors which are cell type specific

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115
Q

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

A

Primary response

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116
Q

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

A

Secondary response

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117
Q

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

A

Signal transduction

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118
Q

What are the three general classes of cell surface receptors?

A
  1. Ion channel coupled receptors 2. G-protein coupled receptors 3. Enzyme couple receptors
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119
Q

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)

A

Ion channel coupled receptor

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120
Q

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

A

G protein coupled receptor

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121
Q

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

A

Enzyme coupled receptors

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122
Q

What kind of coupled receptor is this?

A

G- Protein

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123
Q

What kind of coupled receptor is this?

A

Enzyme

124
Q

What kind of coupled receptor is this?

A

Ion channel

125
Q

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

A

G-protein-coupled or enzyme-coupled receptors

126
Q

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?

A

Secondary messenger

127
Q

What is the function of the secondary messengers?

A

To spread the signal to distal portions of the cell

128
Q

What are some examples of second messengers?

A

Cyclic AMP, calcium, and diacylglycerol

129
Q

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

A

Transduce the original signal throughout the cell

130
Q

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

A
  1. Relay 2. Scaffold 3. Convert 4. Amplify 5. Integrate 6. Anchor 7. Modulate
131
Q

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

A

Phosphorylation or GTP binding

132
Q

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

A

Switches

133
Q

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

A

Between the off and on forms

134
Q

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

A

Protein kinases

135
Q

(Phosphorylation) What are responsible for removing phosphate groups?

A

Protein phosphatases

136
Q

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

A

Phosphorylation cascades

137
Q

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?

A

Relay

138
Q

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

A

Often: serine or threonine; Less often: tyrosine

139
Q

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

A

Monmeric GTP binding proteins

140
Q

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

A

The transduction of the signal

141
Q

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

A

Its inactivation and termination of the signal

142
Q

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

A

GEFs and GAPs

143
Q

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

A

GEFs

144
Q

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

A

GAPs

145
Q

Identify the molecular switches (A and B)

A

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

146
Q

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

A

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

147
Q

It is the phosphorylation at two different sites on protein Y that

A

The propagation of downstream signaling.

148
Q

http://o.quizlet.com/ht4dPCL3sVdzWDZgJbtirA.png

A

results in what?

149
Q

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

A

Complex biological responses (cell survival, growth and proliferation)

150
Q

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

A

These two pathways converge at a single protein

151
Q

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

A

Coincidence detector

152
Q

When is the only time that coincidence detector is activated?

A

When both extracellular signals are present simultaneously

153
Q

What kind of proteins promote intracellular signaling?

A

Large intracellular scaffold proteins

154
Q

What proteins function to hold a number of signal proteins together into a large complex to facilitate the sequential, efficient and selective propagation of the appropriate intracellular response while avoiding the cross activation of other signaling pathways?

A

Scaffold proteins

155
Q

For some signaling pathways the intracellular signaling proteins (scaffolds) are never associated with the scaffold protein or all the time?

A

All the time

156
Q

Which side (A or B) has activated intracellular signaling proteins?

A

B

157
Q

For some signal pathways, the assembly of signaling complexes occurs only after an extracellular signal is bound to what?

A

The receptor protein

158
Q

Signaling complexes typically form where?

A

On the intracellular domain of an activated receptor

159
Q

The close association of signaling proteins promotes what?

A

The efficient transfer of the signal

160
Q

When does the protein complex disassemble? (two answers)

A

When the extracellular signal is terminated and the receptor is not longer activated

161
Q

Activated plasma membrane receptor can result in the

A

Phosphoinositides

162
Q

http://o.quizlet.com/OwdLjsPHld8HfPZV1dul1Q.png

A

hyperphosphorylation of what?

163
Q

What can act as docking sites for intracellular signaling proteins promoting their interaction and stimulating downstream signal activation?

A

Hyperphosphorylated phospholipids

164
Q

Intracellular signaling pathways can be controlled by what kind of feedback loops?

A

Positive and negative feedback loops

165
Q

What kind of feedback loop has output from the activated pathway that stimulates its own production?

A

Positive feedback loop

166
Q

What kind of feedback loop has output from an activated pathway acting to inhibit its own production?

A

Negative feedback loop

167
Q

Identify the feedback loops (A and B)

A

A: Positive feeback loop B: Negative feedback loop

168
Q

An activated protein kinase (S) phosphorylates an inactive E kinase to generate a what?

A

An activated E kinase

169
Q

The activated E kinase feeds back in the pathway to promote

A

Its own phosphorylation and activation

170
Q

The phosphorylation of E kinase is counteracted by the activity of a what?

A

A protein phosphatase (I)

171
Q

The biological response of a pathway to a positive feedback loop is dependent on what?

A

The strength of the feedback loop itself

172
Q

What strength of feedback loop is this? The positive signals act to increase the cells response to the initial signal

A

Moderate strength feedback loop

173
Q

What strength of feedback loop is this? The final response produced can be significantly different than in the presence of lower levels of activation.

A

Strong positive feedback loop

174
Q

Strong positive feedback loops can maintain the intracellular signaling response even in the absence of what?

A

The initial extracellular signal

175
Q

Strong positive feedback loops are responsible for activating the transcription of muscle specific transcription factors necessary for triggering what?

A

Muscle cell specification

176
Q

An activated protein kinase (S) phosphorylates an inactive E kinase to generate what?

A

An activated E kinase

177
Q

Activated E kinase then phosphorylates a protein phosphatase which functions to do what two things?

A

Dephosphorylate, and therefore inactivate, E kinase

178
Q

The impact of negative feedback loops are controlled in part by the delay time between activation of the E kinase and phosphorylation of what?

A

The upstream phosphatase

179
Q

(negative feedback) How strong and how long is the cellular response with a short delay?

A

Strong but short lived

180
Q

With a long delay between E kinase activation of the resulting negative feedback, what will happen to its signal response?

A

It will oscillate in its signal response

181
Q

Prolonged exposure to a stimulus decreases a cell’s response to that level of the signal in a process called what?

A

Desensitization

182
Q

Desensitization allows a cell to respond to changes in the concentration of an extracellular signal rather than to what?

A

The absolute level of a stimulus

183
Q

Signal molecule bound receptors can be internalized by the process of what?

A

Endocytosis

184
Q

What happens to the endocytosed receptors?

A

They can be retained in the endosome or trafficked to the lysosome for degradation

185
Q

If the endocytosed receptors are retained in the endosome or are degraded in the lysosome, what happens to the number of plasma membrane receptors?

A

They are reduced

186
Q

Signal bound receptors can also be inactivated by post translational modifications such as what?

A

Phosphorylation, methylation or ubiquitination

187
Q

An inactivation mechanism can block activation of downstream intracellular signaling proteins ultimately blocking what?

A

The propagation of the signal

188
Q

What kind of protein can block the signal transduction process by acting between the activated receptor and the downstream intracellular signaling protein?

A

An inhibitor protein

189
Q

What is the largest family of cell-surface receptors?

A

G Protein coupled receptors (GPCR)

190
Q

Where are GPCRs found?

A

All eucaryotes

191
Q

How many GPCRs found in the sense of smell in humans? How many GPCRs found in the sense of smell in mice?

A
  1. 700 in humans 2. 1,000 in mice
192
Q

GPCR extracellular signaling molecules include what?

A

Proteins, small peptides, amino acid derivatives, and fatty acids

193
Q

What is the structure of a GPCR?

A

7 transmembrane spanning domains

194
Q

All GPCRs use G proteins to relay the signal into the what?

A

The cytosol

195
Q

What is an orphan receptor?

A

A Receptor with no identified ligand

196
Q

Approximately how many human GPCRs are orphan receptors?

A

~150 human GPCRs are ‘orphan receptors’

197
Q

What is this structure?

A

G-Protein-coupled receptor (GPCR)

198
Q

What are GPCRs linked to via G-proteins?

A

Membrane localized enzymes or ion channels

199
Q

G proteins are trimeric GTP-binding protein composed of what three subunits?

A

_, _ and _

200
Q

What is linked to the cytoplasmic side of the plasma membrane via lipid attachments to the _ and _ subunits?

A

Trimeric protein complex

201
Q

The _-subunit has GTPase activity. Is it active or inactive when bound to GDP?

A

Inactive

202
Q

The _-subunit has GTPase activity. Is it active or inactive when bound to GTP?

A

Active

203
Q

Activated GPCRs functions as a what to stimulate the exchange of GDP for GTP by the alpha subunit?

A

Guanine exchange factor

204
Q

G-protein undergoes a conformational change with GTP binding that promotes what?

A

Interaction with downstream target proteins (membrane localized enzymes or ion channels)

205
Q

Downstream activation is mediated by what?

A

Either the _- or __ subunits

206
Q

Activated G-proteins are released from GPCR which allows the receptor to do what?

A

Activate other G-proteins

207
Q

_-subunit association with its target protein stimulates its GTPase activity converting GTP to what?

A

GDP

208
Q

What is the target protein for G-protein GAP (GTPase activating protein)?

A

Regulator of G protein signaling (RGS)

209
Q

What is generated by ATP through the activity of membrane bound adenylyl cyclases?

A

cAMP

210
Q

How do you increase cyclic AMP concentrations?

A

By increasing the activity of adenylyl cyclase over cellular phosphodiesterases

211
Q

Cytosolic cAMP levels are typically low but can be elevated 20 fold with what?

A

Activation

212
Q

cAMP can be converted to 5’ monophosphate by what?

A

Cyclic AMP phosphodiesterases

213
Q

How many adenylyl cyclase isoforms are there in mammals which are most regulated by G-proteins and Ca2+?

A

8

214
Q

GPCRs that act by increasing cAMP are coupled to a stimultory G protein (Gs) which activate or inhibit adenylyl cyclase?

A

Activate

215
Q

Inhibitory G proteins (Gi) activate or inhibit adenylyl cyclase?

A

Inhibit

216
Q

What product is made at A?

A

cAMP

217
Q

What product is made at B?

A

5’-AMP

218
Q

How does the cholera toxin lead to elevated levels of cAMP levels? (3 steps)

A
  1. Catalyzes the transfer of ADP ribose from NAD to the _-subunit of Gs 2. Altered _-subunit can not hydrolyzing its bound GTP 3. Generates a permenantly activated Gs: indefinitely stimulated adenylyl cyclase leads to elevated cAMP levels
219
Q

How does the Pertussis Toxin work?

A
  1. Modifiies the _-subunit of Gi preventing interaction with receptors 2. Since the receptors function as GAPs, modified Gi proteins are never activated (i.e. no exchange of bound GDP for GTP) 3. Therefore, downstream targets are never activated
220
Q

Which toxin (cholera or pertusis) promotes stable activation of Gs _-subunit?

A

Cholera

221
Q

Which toxin (cholera or pertusis) promotes stable inactivation of Gi _-subunit?

A

Pertussis

222
Q

Gs stimulated increases in cAMP generates differing intracellular responses based on what?

A

Cell type

223
Q

Will increases in cAMP levels trigger the same intracellular response in the same cell regardless of the extracellular signal that triggered the increase?

A

Yes

224
Q

Different cells may have a different intracellular response to increased what levels?

A

cAMP

225
Q

What is a serine/threonine protein kinase that functions as a tetrameric protein complex?

A

PKA

226
Q

What are the components of PKA?

A

2 Regulatory subunits and 2 Catalytic subunits

227
Q

What subunit is used for PKA subcellular localization and binding to cAMP?

A

Regulatory subunit

228
Q

What subunit is involved in target protein phosphorylation?

A

Catalytic subunit

229
Q

What is the primary effector protein in cAMP mediated intracellular responses?

A

Protein kinase A, or PKA

230
Q

Increases in cAMP leads to cAMP molecules binding to what subunits?

A

Regulatory subunits

231
Q

cAMP bound induces a change in conformation promoting their release from the what?

A

The tetrameric complex

232
Q

What are activated and able to phosphorylate substrate proteins?

A

Free catalytic PKA subunits

233
Q

How many types of PKA are found in mammalian cells?

A

2

234
Q

Where is PKA type I found?

A

Cytosol

235
Q

PKA type II localized to what locations by its regulatory subunits?

A
  1. Plasma membrane 2. Nuclear membrane 3. Mitochondrial outer membrane 4. Microtubules
236
Q

PKA localization is mediated by its association with specific anchoring proteins called what?

A

AKAPs (A-kinase anchoring proteins)

237
Q

A-kinase anchoring proteins (AKAPs) function to link PKA to what?

A

A component of the cytoskeleton, the membrane of an organelle or another signalling molecule

238
Q

What binds to a G protein coupled receptor triggering a change in its conformation?

A

An extracellular signal

239
Q

The GPCR functions as a GEF simulating the exchange of GDP for GTP by what subunit of its associated trimeric G-protein?

A

The _-subunit

240
Q

Activated G-protein (Gs) activates what?

A

Adenylyl cyclase

241
Q

Activated adenylyl cyclase synthesizes what from ATP?

A

cAMP

242
Q

cAMP binds to the regulatory subunit of PKA triggers what?

A

A change in conformation and its release from the catalytic subunits

243
Q

Activated catalytic subunits of PKA translocate to the what?

A

Nucleus

244
Q

In the nucleus, activated PKA phosphorylates what?

A

The CREB substrate protein

245
Q

What is a gene regulatory protein that binds to specific DNA sequences called “cyclic AMP response element”?

A

CREB

246
Q

Phosphorylated CREB recruits what?

A

CBP (CREB binding protein)

247
Q

What is a transcriptional co-activator that functions to stimulate the transcription of target genes?

A

CBP

248
Q

Phosphorylation of CREB is not required for what?

A

DNA binding

249
Q

Phosphorylation of CREB is required for the recruitment of what?

A

CBP

250
Q

Activated GPCRs function as a guanine exchange factor to stimulate the exchange of GDP for GTP by the alpha subunit.. Activated GPCRs can also activate what?

A

Phospholipase C

251
Q

Phospholipase C cleaves plasma membrane bound

A
  1. A membrane bound diacylglycerol 2. Water soluble inositol 1,4,5 triphosphate (IP3)
252
Q

http://o.quizlet.com/TaQXg1SRpyHODtZQl2xaeg.png

A

phosphatidylinositol 4,5 bisphosphate (PIP2) into what two products?

253
Q

GPCR mediated activation of phospholipase C is through the activation of a what?

A

Gq protein

254
Q

What does diacylglycerol activate?

A

Protein kinase C

255
Q

What does inositol 1,4,5-triphosphate (IP3) release?

A

Ca3+ from the ER

256
Q

What is this?

A

Inositol 1,4,5-triphosphate (IP3)

257
Q

http://o.quizlet.com/f09DZYgfb0s5LL0eRbiO1A.png

A
  1. It diffuses throughout the cytosol 2. At the ER, it opens IP3 gated calcium release channels triggering release of stored calcium increases in intracellular calcium 3. It activates calcium sensitive proteins propagating the original signal
258
Q

What functions to activate protein kinase C?

A

Diacylglycerol

259
Q

activated PKC is dependent on the rise in cytosolic calcium levels triggered by IP3 as calcium binding to PKC promotes its relocation from the cytosol to where?

A

Plasma membrane

260
Q

Plasma membrane bound PKC interacts with phosphotidyl serine and diacylglycerol leading to what?

A

Its activation

261
Q

Activated PKC phosphorylates downstream target proteins propagating what?

A

The original signal

262
Q

What are the three steps in terminating IP3 mediated signaling?

A
  1. Dephosphorylation of IP3 to IP2 by a lipid phosphatase 2. Phosphorylation of IP3 to IP4 by a lipid kinase 3. Removal of cytosolic calcium
263
Q

IP3 levels are decreased by either phosphorylation to generate what or dephosphorylation to generate what?

A

Phosphorylate: IP4 Dephosphorylate: IPs

264
Q

Cytosolic calcium levels are decreased through what?

A

Plasma membrane pumps and organellar pumps

265
Q

All eukaryotic cells contain what kind of pumps that moves calcium out of the cell

A

an ATP-dependent calcium pumps

266
Q

Cells that extensively utilize calcium signaling have an additional calcium pump in their plasma membrane, what is it?

A

The sodium driven calcium exchanger

267
Q

What two organelles contain calcium pumps that remove cytosolic calcium?

A

The ER and the mitochondria

268
Q

What kind of pump does the ER have?

A

ATP dependent calcium pump

269
Q

What pump is located in the inner membrane of the mitochondria and uses the energy stored in the proton gradient for the uptake of calcium

A

The mitochondrial calcium pump

270
Q

What is a key calcium binding protein that is found in all eukaryotic cells?

A

Calmodulin

271
Q

What is the structure of calmodulin?

A

Single polypeptide chain that folds into a dumbell shaped structure (2 globular ends linked through an _-helix)

272
Q

How many calcium ion does calmodulin bind per globular head? How many total?

A

Binds 4 calcium ions; 2 per globular head

273
Q

When does calmodulin undergo a conformational change?

A

With calcium binding (activation)

274
Q

How many calcium ions must bind to trigger the conformational change in calmodulin?

A

2

275
Q

Activated calmodulin does what?

A

It binds to other target proteins activating those proteins

276
Q

What is the function of calmodulin?

A

It regulates enzymes and membrane transport proteins

277
Q

What is a large protein complex composed of 12 subunits?

A

CaM kinase II

278
Q

At the start of the reaction cycle CaM Kinase II is inactive with its amino terminal catalytic domain folded such that it interacts with what domain?

A

Its inhibitory domain

279
Q

An increase in cytosolic calcium levels activates calmodulin which binds to what?

A

CaM kinase II

280
Q

After calmodulin and CaM kinase II binding, a conformational change in CaM kinase II is induced partially activating what?

A

The kinase

281
Q

What activation requires autophosphorylation where the kinase activity of the catalytic domain phosphorylates the inhibitory domain of an adjacent CaM-kinase molecule?

A

Full CaM kinase II

282
Q

Can the fully activated form of CaM kinase II retain its kinase activity even if cytosolic calcium levels fall and calmodulin is released?

A

Yes

283
Q

Fully activated CaM kinase II can phosphorylate target substrate proteins long after what has been terminated?

A

The initial calcium signal has terminated

284
Q

Turning off CaM kinase II requires what to remove the activating phosphorylation on its regulatory domain?

A

Protein phosphatase

285
Q

What can G-proteins do to ion channels in the plasma membrane?

A

Activate or inactivate them

286
Q

If G-proteins activate or inactivate ion channels in the plasma membrane, what can they influence?

A

The membrane potential

287
Q

Give two kinds of regulation that G-proteins can have?

A
  1. Phosphorylation of the ion channel (PKA, PKC or CaM-kinase) 2. Altering the levels of cyclic nucleotides
288
Q

Acetylcholine binds to plasma membrane receptors where?

A

On a muscle cell

289
Q

Acetylcholine binds to plasma membrane receptors on a muscle cell. What happens next?

A

A Gi protein is activated

290
Q

After the Gi protein is activated. What happens next?

A

The _-subunit of the G protein inhibits adenylyl cyclase; the __ subunit opens plasma membrane K+ channels

291
Q

Opening of K+ channels leads to increased leakage of what? where?

A

Potassium ions out of the cell

292
Q

What is the end result of acetylcholine?

A

Muscle cell depolarization is more difficult reducing the rate and force of muscle contraction

293
Q

G proteins can also impact cyclic nucleotide gated channels by altering the levels of what?

A

Cyclic nucleotides (cGMP)

294
Q

What is the function of Gs?

A

Activates adenylyl cyclase; activates Ca2+ channels

295
Q

What is the function of Gi?

A

Inhibits adenylyl cyclase; activates K+ channels

296
Q

What is the function of Gq?

A

It activates phospholipase C-beta

297
Q

What are the three mechanisms of GPCR inactivation?

A
  1. Receptor inactivation 2. Receptor sequestration 3. Receptor down-regulation
298
Q

Receptor alteration such that interaction with G proteins is lost?

A

Receptor inactivation

299
Q

Receptors are targeted for lysosomal destruction after internalization

A

Receptor down-regulation

300
Q

Receptors are moved to an intracellular compartment away from ligand

A

Receptor sequestration

301
Q

What alters the quantity of the receptor or the activity of the receptor?

A

Desensitization

302
Q

Inactivation depends on phosphorylation of the receptor by what?

A

PKA, PKC or a GPCR kinase

303
Q

Only what kind of receptors can be phosphorylated (and therefore undergo desensitization) as it is this receptor that activates these kinases

A

Activated receptors

304
Q

Phosphorylated GPCRs can interact with arrestin proteins and arrestin can prevent what? Blocking what?

A

GPCR interaction with downstream G-proteins blocking propagation of the signal.

305
Q

Arrestin binding can also promote what kind of endocytosis?

A

Clathrin-dependent

306
Q

What three things can happen to interalized receptors?

A
  1. Dephosphorylated and returned back to the plasma membrane 2. Remain sequestered in endosomal compartments 3. Targeted to the lysosome for degradation

Eukaryotic Cell Biology (7 decks)

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