Final: Ch 15 G-Protein Coupled Receptors Flashcards Preview

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Flashcards in Final: Ch 15 G-Protein Coupled Receptors Deck (71):
1

what is a G-protein

GTP-binding protein

bind GTP/GDP

active when bound to GTP, inactive when bound to GDP

2

regulation of G-protein genes

transcriptional regulation using TF (binds to promoter)

post-translational regulation/modification

3

examples of post-transcriptional regulation of G-protein genes

alternative splicing

capping

polyadenylation

RNAi

4

G-proteins are anchored in the cell membrane when...

GDP bound --> ligand binds --> GTP binds to alpha subunit

5

4 things GPCR signal transduction pathways have in common

receptor with 7 transmembrane alpha helices

coupled trimeric G-protein switch

membrane-bound effector protein

proteins for feedback regulation and desensitization of the pathway

6

where are the N and C termini of GPCR

N-terminus on extracellular face

C-terminus on cytosolic face

7

B-adrenergic receptors

bind hormones like epi and nor-epi

8

can different subtypes of GPCR bind the same hormone and have different effects?

yes

ex. epinepherine (in heart increases contraction, in smooth muscle relaxes)

9

what happens in fight or flight

adrenal gland releases Epi to bind B-adrenergic GPCR in liver/muscle cells

stimulate glycogen breakdown to glucose

high epi in blood

10

trimeric G-proteins 3 subunits

alpha

beta + gamma (complexed together)

linked to membrane by lipids

11

in resting state, G-alpha subunit has a bound ___ and is complexed to _____

GDP, complexed to G-betagamma

12

binding of ligand to GPCR changes conformation of the receptor and allows...

the receptor to bind to G-alpha subunit --> release GDP

GTP binds G-alpha --> release of receptor and G-betagamma

G-alpha binds effector protein

13

how to detect GPCR-mediated dissociation of the G protein

FRET - fluorescence energy transfer

14

all effector proteins in GPCR pathway are either...

membrane bound ion channels

membrane bound enzymes that catalyze formation of 2nd messengers

15

which subunit of the G-protein determines its function?

G-alpha

ex. G-alpha S activates adenylyl cyclase to increase cAMP

G-alpha i inhibits adenylyl cyclase to decrease cAMP

16

one of the simplest cellular responses to a signal is the opening of...

ion channels

ex. open ligand-gated ion channels for neurotransmitters

17

many nt receptors are...

GPCR whose effector proteins are Na or K channels

18

mAChR are a type of GPCR found in _____ muscle

cardiac muscle

19

what happens when mAChR are activated

G-betagamma opens K+ channel (usually G-alpha)

slow heart rate when K+ channels open

efflux of K+ causes hyperpolarization and slows contraction

20

cones are for ____, rods are for ____/______

color, black/white

found in retina, signals processed by visual cortex

21

rhodopsin

light-sensitive GPCR (opsin) that helps rods sense light

G-protein called Transducin (G-alpha-t)

photon-absorbing pigment called retinal

22

how does rhodopsin differ from other GPCRs

absorption of a photon of light is the signal (by retinal), not binding of ligand

23

what happens when rhodopsin absorbs a photon of light

cis --> trans in retinal form causes conformational change in GPCR opsin

rhodopsin binds G-alpha-t subunit and exchanges GDP for GTP

G-alpha-t removes inhibitory gamma segments from phosphodiesterase (PDE), which turns cGMP --> GMP

24

activation of rhodopsin by light leads to the closing of ____-gated cation channels

cGMP

causes membrane potential to become more inside negative (hyperpolarization-less nt released)

25

in the dark the membrane potential of a rod cell is...

-30mV

this is a state of depolarization so in the dark, the rod cell is constantly secreting nt

26

why is there a constant state of depolarization of resting rod cells

large number of open nonselective ion channels that let Na and Ca in

27

to close the cation channels, the 2nd messenger _____ is turned into

cGMP --> GMP

upon absorbing light, cGMP PDE hydrolyzes cGMP to GMP

cGMP releases from gated channels, closing them

28

the ____ level of cGMP in the dark keeps cGMP gated cation channels open, in the light...

high

decrease in cGMP concentration by PDE causes closing of channels and less nt release

29

what makes the rhodopsin signal transduction pathway so sensitive?

signal amplification of the photon of light

each activated opsin activates 500 G-alpha-t molecules which activate the PDE

30

what GAP proteins inactivate G-alpha-t GTP

RGS-9 and G-beta-5

hydrolyze GTP --> GDP so PDE is inactivated again

31

Rhodopsin kinase

phosphorylates active rhodopsin

arrestin binds after 3 phosphates and prevents transducin activation (G-alpha-t)

32

how do rod cells adapt to varying levels of ambient light -- visual adaptation

adjusting trafficking of arrestin and transducin

80% of G-alpha-t and G-betagamma move out of the outer segment and 80% of arrestin moves into outer segment in 10 min of moderate light

prevents PDE activation

33

adenylyl cyclase synthesizes ____ from ____

cAMP, ATP

34

cAMP activates a _____

kinase

35

glycogen

a storage polymer of glucose

broken down in liver/muscle cells in response to the hormone epinerpherine

36

all of the effects of cAMP are mediated through activation of which kinase

protein kinase A (cAMP dependent protein kinase)

binding of cAMP opens catalytic active site

37

degradation of glycogen is called

glycogenolysis

stepwise removal of glucose residues from one end of the polymer by glycogen phosphorylase

38

in the liver, glycogen stores are broken down to ....

glucose, which is released into the blood and transported to tissues like muscle and brain for energy

39

2 ways epinerpherine stimulated activation of adenylyl cyclase --> higher cAMP --> PKA activation enhances conversion of glycogen to glucose

inhibit glycogen synthesis enzymes

stimulating glycogen degradation enzymes

40

what does PKA do

phosphorylates and inactivates glycogen synthase (GS), the enzyme that synthesizes glycogen

phosphorylates the inhibitor of phosphoprotein phosphatase (IP) to inactivate it (so glycogen phosphorylase kinase can break down glycogen)

41

in adipose cells, what does activation of PKA do

phosphorylation of a lipase that hydrolyzes stored triglycerides to FA and glycerol for energy

42

is there signal amplification in the cAMP-PKA pathway?

yes

GPC hormone receptors are able to diffuse rapidly in the plasma membrane

a single epinerpherine-GPCR complex activates up to 100 G-alpha s molecules --> adenylyl cyclase and so on

43

activation of PKA also stimulates the expression of...

many genes, including CREB

leads to long-term effects

44

CRE

cAMP response element

binds the phosphorylated form of the TF CREB

45

all genes regulated by PKA have ____

CRE

binds the phosphorylated form of the TF CREB

46

CREB TF

CRE-binding protein

found in nucleus

47

genomic response of PKA

catalytic subunit of PKA targets CREB in nucleus and phosphorylates it

CREB binds to distal promoter (response element) of target gene and recruits co-regulator

stimulates gene transcription

48

a ligand (hormone) can have a non ______ response, a ______ response, or both

genomic, genomic

49

what is A kinase-associated protein

an anchoring protein that binds PKA to specific locations so it is activated in only those locations

ex. heart muscle cells have AKAP15 near Ca channels

50

AKAP in the outer nuclear membrane

localizes PKA and cAMP PDE to outer nuclear membrane

helps catalytic subunits of PKA enter nucleus

allows for negative feedback regulation

51

3 ways to down-regulate signaling through the GPCR/cAMP/PKA pathway

affinity of receptor for ligand is decreased when GDP is replaced by GTP in G-alpha

intrinsic GTPase activity of G-alpha hydrolyzes GTP --> GDP (hydrolysis rate increased when G-alpha binds adenylyl cyclase)

cAMP PDE hydrolyzes cAMP --> AMP to end cellular response

52

most GPCRs are also down-regulated by ______-_________

feedback repression

end product blocks early step in pathway

53

B-arrestin

assists endocytosis of cell-surface receptors

54

phospholipase C (PLC)

enzymes that hydrolyze a phosphoester bond to yield 2nd messengers that raise cytosolic Ca2+ levels and remodel actin

activate protein kinase C

55

protein kinase C (PKC)

affect cellular growth and differentiation

56

important 2nd messengers are derived from the membrane lipid, ______________

phosphatidylinositol (PI)

PI --> PIP2

57

PLC cleaves PIP2 into...

DAG (diacylglycerol) and IP3 (inositol triphosphate)

58

DAG is associated with the ______ while IP3 freely _______ in the cytosol

membrane, diffuses

59

GPCR that activate PLC increase cytosolic ____ concentration even when the ions are absent from the extracellular fluid

Ca2+ concentration

PLC cleaves PIP2 into IP3, which opens IP3 gated-Ca channel in ER lumen

60

what does DAG activate

protein kinase C - moves to cytosolic leaflet

61

activation of PKC has what effects

growth and metabolism

phosphorylates TF

ex. in liver cells, PKC regulates glycogen metabolism

62

calmodulin

small cytosolic switch protein that mediates many cellular effects of Ca ions

63

glycogen breakdown and synthesis is coordinately regulated by which two second messengers

Ca2+ and cAMP

levels are regulated by neural and hormonal stimulation

64

why is nitroglycerin used to treat angina

decomposes to nitric oxide (NO), which relaxes smc in the heart

65

what is the allosteric effect (Hb) -- positive cooperativity

Hb binds oxygen -- increased affinity in lungs, less in tissue

more binding increases affinity

creates a more dramatic switch

66

basic epi GPCR pathway

epi + GPCR --> GTP G-alpha

activate adenylyl cyclase --> higher cAMP

cAMP activates PKA to stimulate breakdown of glycogen OR phosphorylation of TF in the nucleus (ex. CREB)

67

do G proteins usually have short-term or long-term effects?

short-term

modify existing enzymes or ion channels

68

structure of inactive PKA

tetramer of 2 regulatory subunits and 2 catalytic subunits

each R subunit binds the active site of a C subunit to inactivate

69

how is inactive PKA turned on

2 cAMP binds each R subunit

conformational change causes R subunits to release C subunits

70

glycogen phosphorylase kinase

glycogen --> glucose activates glycogen phosphorylase

activated by high [Ca2+], PKA

71

glycogen synthase

stimulates glycogen formation

inhibited by PKA, PKC