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Cell biology > Plasma membrane receptors which couple to heterotrimeric G proteins. > Flashcards

Plasma membrane receptors which couple to heterotrimeric G proteins. Flashcards

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1
Q

What does GPCR stand for?

A

G-protein coupled receptor.

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2
Q

Are GPCR proteins a type of metabotropic receptor?

A

Yes. But they often indirectly cause channels to open.

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3
Q

What type of G-protein do GPCR receptors entail?

  • Monomeric?
  • heterotrimeric
A

heterotrimeric:

alpha, beta, gamma.

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4
Q

How many genes in percentage and number deal with GPCRs?

A

~800 genes
~4% of all genes

and 40-50% of clinical drugs affect this region

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5
Q

In a GPCR what does the Galpha subunit do?

A

It functions as the actual molecular switch. It possesses intrinsic GTPase activity

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6
Q

Which of the three subunits of a heterotrimeric g protein are imbedded in the membrane?
Through what means?

A

alpha and gamma

Prenylation

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7
Q

Where in the alpha subunit does the GTP/GDP reside?

A

In the AH domain!

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8
Q

How does the beta subunit stay localized with the other subunits? (since it is not connected to the membrane)

A

It dimerizes with the gamma subunit.

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9
Q

What is true when the Galpha subunit is bound to GDP?

A

It is mostly inactive.

It has a high affinity for beta-gamma subunit.

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10
Q

What is the difference between a GPCR and a heterotrimeric G protein?

A

A GPCR is a receptor. It is coupled and interacts with a heterotrimeric G-protein.

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11
Q

How does the GPCR interact with the heterotrimeric G protein?

A

If the GPCR is ligand activated or constitutively active, then it will act as a GEF. It will remove GDP, allowing GTP to bind and more importantly separation of the Galpha subunit and the G-beta-gamma subunits. Exposing the interaction surfaces.

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12
Q

What is the concentration of GTP relative to GDP in the cytosol?

A

GTP ~.5mM

GDP ~.05mM

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13
Q

How is it possible that in some cells the Galpha and Gbetagamma of activated G-proteins do not dissociate?

A

While they do not disassociate, binding of GTP results in a shift which exposes the interactive surfaces of alpha and beta.

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14
Q

What does adenylyl cyclase do? It is activated or inhibited by which G subunit?

A

It turns AMP to cAMP.

It is activated by Galpha(s) subunit

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15
Q

How are VGSCs affected by the Gbetagamma subunit?

A

Inhibited.

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16
Q

Effector antagonist:

A

Downstream effector blocks signaling of G-protein subunit. Negative feedback. (do NOT use a GAP mechanism)

17
Q

GRKs (G protein-coupled receptor kinases) do what?

A

They phosphorylate GPCRs.

18
Q

How many types of GRKs are there?

A

At least three
GRK1
GRK2
GRK3

19
Q

Name to protein kinases which are not GRKs which phosphorylate GPCRs.

A

Protein Kinase A (PKA)

Protein Kinase C (PKC)

20
Q

Only _______ GPCRs are phosphorylated by GRKs.

A

activated.

21
Q

What are the steps of arrestin mediated internalization?

A

An activated GPCR is phosphorylated by a GRK (or PKA or PKC).
After phosphorylation, arrestin can bind, inhibiting GPCR from interacting with G-proteins.
Arrestin is an adaptor for clathrin, which causes endocytosis.
internalized GPCRs can be destroyed in a lysosome, or signal in a different what after arrestin recruits intracellular signaling proteins.

22
Q

What are the four mechanisms to block or reduce signaling through GPCRs?

A

Inactivation: involves covalent modification of GPCR proteins so they lose GEF activity.
Sequestration: GPCRs are endocytosed into recycling endosomes, and are not exposed to their agonist, can be sent back the the PM.
Desensitization: same mechanism as inactivation.
Down-regulation: GPCRs are endocytosed and destroyed within lysosomes.

23
Q

Why are yeast used as a model to study GPCRs?

A

GPCR & and heterotrimeric g-proteins are evolutionarily conserved mechanisms between yeast and humans.

24
Q

Yeast mating factor is similar to what human hormone?

What does it do?

A

It is similar to LH (produced by the anterior pituitary)

Causes a behavior in haploid yeast called shmooing, where they extend in the direction of yeast mating factor.

25
Q

What type of receptor system deal with yeast mating factor?

A

GPCR agonist.

26
Q

How long does the intrinsic hydrolytic ability of alpha subunit take to GTP–>GDP?

A

~10 minutes

27
Q

What do (RGS) Regulators of G protein signaling do?

A

They act as GAPs. by catalyzing hydrolysis GTP –> GDP in Galpha subunits. Once the Galpha has GDP bound, it regains affinity for a Gbetagamma subunit.

28
Q

How many distinct RGS proteins exist? How do they tie in with visual phototransduction?

A

~30

allow for rapid down regulation of visual signal so another visual signal can be perceived.

29
Q

How much do RGS accelerate GTP hydrolysis?

Do they affect the onset and termination?

A

1000x

yes

30
Q

Effector gap:

A

Form of negative feedback where a downstream effector will act as gaps for the Galpha subunit (PLC-beta1 does this for gap Galpha(q)/11)

31
Q 
Name the Galpha subunits downstream effector:
Galpha(s)
Galpha(i/o)
Galpha(g/11)
Galpha(12/13)
A

Galpha(s): stimulates adenylyl cyclase
Galpha(i/o): inhibits adenylyl cyclase
Galpha(q/11): stimulates phospholipase C
Galpha(12/13): activates rhoGEF

32
Q

What does rhoGEF do?

A

It is the GEP for Rho/rac/cdc42 family, which regulation cytoskeleton and therefor shape and locomotion.

33
Q

Cholera toxin does what mechanistically?

A

ADP-ribosylation of Galpha(s), this blocks GTP hydrolysis, keeping constitutive activity. Causes diarrhea, cholera.

34
Q

Pertussis toxin does what mechanistically?

A

PTX causes Galpha(i) to by ADP-ribosylated, blocks activation of G(i/o) by GPCR. causes whooping cough.

35
Q 
what do they do?
Galpha(s):
Galpha(olf):
Galpha(i/o):
Gbetagama:
Gbetagama:
Galpha(T):
Galpha(q/11):
A

Galpha(s): stimulates adenylyl cyclase (AC)
Galpha(olf): activates olfactory adenylyl cyclase (AC)
Galpha(i/o): inhibits AC
Gbetagama: activate GIRK potassium channels.
Gbetagama: inhibits VGCaCs.
Galpha(T): direct activation of phosphodiesterase in rods and cones
Galpha(q/11): directly activates phospholipase beta1

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