Lecture 15: Cell communication-signalling through G-protein coupled receptors Flashcards

1
Q

Why is intercellular communication necessary?

A
  • Cellular differentiation and specialization
  • Growth stimulation or termination
  • Tissue formation
  • Integration of metabolism
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2
Q

General Signaling Pathway?

A
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3
Q

What are the three types of effector proteins?

A
  • metabolic enzyme
  • transcription regulatory protein
  • cytoskeletal protein
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4
Q

4 types of signal distribution?

A
  • contact-dependent
  • paracrine/autocrine
  • synaptic
  • endocrine
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5
Q

What is the fast effect of signaling?

A
  • altered protein function
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6
Q

What is the slow effect of signaling?

A
  • altered protein synthesis
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7
Q

Endocrine signals are ___ in concentration and its receptors are ____ affinity

A

low conc

high affinity

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8
Q

Synaptic signals are ___ in concentration and its receptors are ____ affinity

A

high conc

low affinity

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9
Q

Chemical types of signaling molecules

A
  • Amino acid derivatives
  • Nucleotides
  • Lipids

– Steroids

– Arachidonic acid metabolites

-eicosanoids

– Retinoids

  • Peptides
  • Gases

– Nitric Oxide (NO)

– Carbon Monoxide (CO)

• Protons

– C. elegans muscle

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10
Q

Amino Acid derived signals are ____

A

shorter lifespan, more paracrine-like

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11
Q

Steroid signals are relatively ____ lasting

A

long

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12
Q

Steroid signals are derived from ____’s structure

A

cholesterol

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13
Q

Eicosanoids are derived from ___’s structure

A

arachodonic acid

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14
Q

Peptide hormones include:

A
  • Pituitary hormones
  • hypothalamic hormones
  • thyroid hormones
  • digestive hormones
  • pancreatic hormones
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15
Q

Nitric Oxide is a ____

A

vasodilator

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16
Q

Nitric oxide synthase transforms ____ into NO and citroline

A

arginine

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17
Q

NO diffuses out of the ____ cell into the ____ cell

A

endothelial to smooth muscle

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18
Q

What is the name of the cytosolic intracellular receptor NO binds to?

A

guanyl cyclase

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19
Q

Membrane soluble signals (those that bind to intracellular receptors) require ____ to navigate the aqeous environment outside the cells

A

carrier proteins

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20
Q

Cell-surface receptors usually bind to ____ signals.

A

hydrophilic

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21
Q

Intracellular receptors

A
  • Nuclear receptor superfamily
  • Steroid hormone receptors are ligand-activated transcription factors
  • They are modular in construction

– Ligand binding domain

– DNA-binding domain

– Variable region

• Generally function with other binding partners

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22
Q

What are the three domains of a steriod receptor? where are they located?

A

N-terminus: transcription-activating domain

Middle: DNA-binding domain

C-terminus: ligand-binding domain

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23
Q

Response induced by steroid hormone receptor activation

A
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24
Q

The presence of a hormone or ligand is sensed by an ____

A

integral membrane protein receptor

• This information is communicated across the cell membrane and transmitted by intracellular signaling molecules.

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25
Q

Small intracellular mediators are also referred to as ____

A

“second messengers”

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26
Q

Second messengers illicit various cellular responses:

A
  • Activate or inhibit specific protein targets
  • Increase or decrease gene transcription
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27
Q

3 types of cell surface receptors?

A
  • Ion channels coupled receptors
  • G-protein coupled receptors
  • Enzyme-linked receptors
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28
Q

A nicotinic acetylcholine receptor is___

A

an ionictropic receptor

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29
Q

A muscarinic acetylcholine receptor is ____

A

a metabotropic receptor

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30
Q

Enzyme-linked receptors____

A

dimerize to form catalytic domains

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31
Q

Common Second Messangers:

A
  • cAMP
  • cGMP
  • DAG (diacylglycerol)
  • IP3 (inositol triphosphate)
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32
Q

cAMP

A

activates protein kinase A (PKA)

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33
Q

cGMP

A

Activates protein kinase G (PKG) and opens cation channels in rod cells

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34
Q

DAG

A

activates protein kinase c (PKC)

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35
Q

IP3

A

Opens ca2+ cannels in the ER

36
Q

What are the two forms of molecular switches in singaling?

A
  • signaling by phosphorylation
  • signaling by GTP binding
37
Q

A intracelllular signaling protein is ON when it’s ____ or bound to____. It’s OFF when it’s ____ or ____

A

ON- phosphorylated or bound to GTP

OFF- dephosphorylated or bound to GDP

38
Q

protein kinases ___ a phosphate from ___

A

remove a phosphate from ATP and add it to the intracellular signaling protein

39
Q

protein phosphatases ____ the intracellular signaling protein

A

dephosporylate (remove a phosphate)

40
Q

GEF proteins-

A

-help GTP to bind by ejecting GDP

41
Q

GAP

A

cuts of the terminal phosphate of GTP (Deposphorylates it to GDP)

42
Q

Tyrosine Kinase receptors

A

-add phosphate from ATP to tyrosine residues

43
Q

Which amino acid side chains get phosphorylated?

A

Tyrosine (Y), Serine (S), Threonine (T)

44
Q

Signal integration

A

Multiple signals and their receptors can affect the same intracellular signaling molecule

45
Q

What are the three types of intracellular signaling complexes?

A
  • preformed signaling complex on a scaffold protein
  • assembly of signaling complex on activated receptor
  • assembly of signaling complex on phosphoinositide docking sites
46
Q

What signaling pathway involves all three types of intracellular signaling complexes?

A

The insulin signaling complex

47
Q

Receptor sequestration

A
48
Q

Receptor down-regulation

A
49
Q

receptor inactivation

A
50
Q

Inactivation of signaling protein

A
51
Q

Production of inhibitory protein

A
52
Q

General G-protein activation

A
53
Q

G-protein coupled receptors (GPCRs)

A
  • Seven transmembrane domains
  • Responds to very diverse ligands

– Photons

– Peptide hormones

– Eicosanoids

– Amino acid derivatives

• Largest family of cell surface receptors in eukaryotes

– >1,000 devoted to smell alone in mice

• About half of all known drugs work through Gprotein coupled receptors

54
Q

For GPCRs the C-terminus is on the ____ side and the N-terminus is on the ____ side.

A

C=cytosolic side

N=extracellular side

55
Q

The βγ subunit…

A

function as a unit and has never been shown to be separate in the cell.

56
Q

The α-subunit is….

A

postranslationally modified by the addition of myristic acid to the N-terminus.

57
Q

The γ-subunit is….

A

postranslationally modified by the addition of a polyisoprenoid, usually farnesyl.

58
Q

These hydrophobic modifications (to the βγ subunit)…

A

serve to localize the complex to the membrane, its site of action.

59
Q

the α-subunit has…

A

A ras domain and an AH (alpha-helical) domain

60
Q

On a G-protein, the gdp binding spot is on the ___ subunit

A

alpha

61
Q

β-adrenergic receptor is a…

A

G-protein coupled receptor

62
Q

G-protein effectors:

A
  • Ion channels
  • Adenylyl cyclase
  • Phospholipase Cβ
  • cGMP Phosphodiesterase
63
Q

Adenylyl cyclase produces _____

A

cAMP

64
Q

The ___ subunit of G-protein interacts with adenylate cyclase

A
65
Q

Adenylate kinase has ___ catalytic domains.

A
66
Q

How does cAMP produce a cellular response?

A

It binds to a protein kinase (PKA)

67
Q

Activated PKA bind to ____ to produce___

A

inactive CREB, CREB -binding protein (CBP)

68
Q

CBP binds to ___

A

cyclic AMP response element (CRE) which activates a target gene for transcription

69
Q

Acute response of cAMP

A

-phosphorylation of protein involves in glycogen metabolism

70
Q

Delayed response of cAMP

A
  • increase in synthesis of the somatostatin gene
71
Q

Ser/Thr protein phosphatases ____ the action or protein kinases

A

reverse

72
Q

Four types of protein phosphatases

A

-Type I (dephosphorylates most PKA substrates)

– Type IIA (broad specificity, main PPTase)

– Type IIB (aka Calcineurin, regulated by Ca2+)

– Type IIC (minor player)

73
Q

G-protein activation of PLCβ

A

• Phospholipase C beta

  • PLCβ is activated by specific Gα-subtypes
  • Gqα, Goα, and Goβγ activate PLC
74
Q

Phosphatidylinositides

A
  • phospolipase release IP3 from glycerol back bone, forming IP3 and diacylglycerol
  • diacylglycerol (DAG) activates PKC
  • IP3 releases ca2+ from the ER
75
Q
A
76
Q

Calcium is sometimes used as a ____

A

second messenger

77
Q

Positive and negative feedback produce ____

A

calcium waves

78
Q

Ca2+ homeostasis is maintained by…

A
  • Membrane pumps:
    • Na+ driven Ca2+ exchanger
    • Ca2+ Pump
79
Q

What three mechanism help to maintain low cytosolic Ca2+ levels?

A
  • Ca2+ pump in ER membrane
  • Ca2+ binding molecules in the cytoplasm
  • active Ca2+ import into the mitochondria
80
Q

Ca2+ signaling effects are mediated by which three Ca2+ binding proteins?

A
  • Troponin C
  • Synaptotagmin
  • Calmodulin
81
Q

Troponin C

A

– Muscle contraction

82
Q

Synaptotagmin

A

– Neurotransmission

83
Q

Calmodulin

A

– Multipurpose Ca2+ receptor involved in many responses

– Binds 4 Ca2+ ions, need two or more or adopt an active conformation

84
Q

How does Calmodulin change conformation upon Ca2+ binding?

A

Its two domains wrap around its target protein

85
Q

What are the three types of Ca2+-Calmodulin-dependent protein kinases?

A
  • Narrow Substrate specificity
    • Myosin light chain kinase (smooth muscle contraction)
    • Phosphorylase kinase (glycogen breakdown)
  • Broad substrate specificity
    • CaM-Kinase II
86
Q

What does activated CaM kinase II do?

A
  • Its mechanism of activation allows past calcium influxes to be “remembered”
  • The enzyme also changes its activity in response to calcium oscillations

– It can react to frequency and amplitude of calcium spikes

• Important for learning an memory in the brain

87
Q

_____ can sense Ca2+ oscillations

A

CaM kinase II