Create
Learn
Share

GPCRs

rename
imissyou419's version from 2016-12-17 06:00

Section

Question Answer
When you take NSAIDs, what happens?NSAIDs block activity of COX, less prostagladin synthesis (PGE2) to minimize pain and inflammation (prostanoids act on GPCRs)
Histamine receptor plays a role inallergies and ulcers
Serotonin receptor (5'HT) plays a role inpyschosis, anxiety, migraines
Angiotensin receptor plays a role inhypertension
Adrenoreceptor plays a role in hypertension, congestive heart failure, asthma
Structure7 TM, 3 intracellular loops, 3 extracellular loops, N- terminal, C-terminal
Transmembrane spanning domainsligand binding
Amino-terminal domainligand binding, post-transcriptional modification - since its extracellular
Intracellular loop domainsG-protein coupling, interactions with G-protein independent signalling proteins, regulatory protein interactions (GRKs)
Carboxyl-terminal domainsG-protein coupling, interactions w/ G-protein independent signalling, regulatory protein interactions (GRKs)
Gs alphaactivates adenylyl cyclase, activates Ca2+ channels
Golf alphaactivates adenylyl cyclase in olfactory sensory neurons
Gi alpha inhibit adenylyl cyclase
Gi beta gammaactivate K+ channels
Go beta gammaactivates K+ channels, inactivates Ca2+ channels
Go alpha, beta and gammaactivates PLC-beta
Gt (transducin) alphaactivates cGMP phosphodiesterase in vertebral rod cells
Gq alphaactivates PLC-beta
G12/13 alphaactivates Rho family monomeric GTPases via Rho-GEF to regulate actin cytoskeleton
Ca2+ oscillation functions1) regulate release of insulin from pancreas (exocytosis), 2) activate extracellular signal regulated kinases -> ERK, MAPK pathway, 3) activate PKC, 4) selectively activate different transcription factors -> NFAT - activated by HIGH frequency oscillations, NFkappaB - activated by LOW frequency oscillations
NFAT activated by ____ frequency Ca2+ oscillationshigh
NFkappaB activated by ____ frequency Ca2+ oscillationslow
Dopamine couples to what receptor and then to what?Dopamine couples to dopamine receptor which can couple Gs (D1) and Gi (D2) [looks like SISI]
LPA couples to what receptor and then to what?LPA couples to Gq and G12/13 and Gi (IQ of 12/13)
G beta gamma functions (4)1) activate ion channels, 2) activate PLC, 3) regulate adenylyl cyclase activity, 4) modulate receptor function by controlling location of GRKs that blunt receptor activity (it binds GRKs and regulate its translocation to PM)
At1AR (angiotensin receptor) has ___ basal activitylow
mGluR1 (metabotropic glutamate receptor) has ___ basal activityhigh (through measuring IP3 formation)
thyroid adenomasmutation to thyroid stimulating hormone receptor (increased stimulation = cancer)
retinis pigmentosamutation to rhodopsin leading to progressive death of rods -> loss of peripheral vision
nephrogenic diabetes insipidussimple loss of function or constitutive desensitization of argine vasopressin receptor 2
central hypogonadrotropic hypogonadismsimple loss of function of gonadotroponin-releasing hormone receptor
central hypothyrodismsimple loss of function of thyroid-releasing hormone receptor
short statureloss of basal activity for ghrelin receptor
extreme obesityloss of basal activity for melanocortin 4 receptor
nephrogenic syndrome of inapproperiate anti-diuresisincreased constitutive activity of arginine vasopressin receptor 2
male-limited precoccious pubertyincreased constitutive activity of luteinizing hormone receptor
precocious pubertydecreased desensitization of KISS 1 receptor
Class A GPCRB-arrestin TRANSIENTLY bind to receptor and it falls off in cytosol; rapid recycling of GPCR to cell surface (after phosphate removed by phosphotases, ligand removed @ endosome), to begin another round of signalling OR undergo downregulation/degradation
Class B GPCRB-arrestin STABLY bind to GPCR; slow recycling? and/or targeted for degradation in lysosomes
Class A GPCR examplesB2 adrenergic receptor, LPA1 receptor
Class B GPCR examplesAT1ar (angiotensin receptor), mGluR1a (metabotropic glutamate receptor) - BATM
Angiotensin IIincrease IP production (increase Ca2+ -> increase HR and contractility)
Homologous desensitizationagonist only affects the activity of its own receptor (not affecting other receptors), role of B-arrestin/GRKs
Heterologous desensitizationoccurs with activation of PKA or PKC which desensitize receptors for other ligands as well but ligand does not need to be there
How does B-arrestin associate with AP2?B2-adaptin subunit of AP2
Clathrin triskelion structure3 heavy chain, 3 light chains, globular domains of heavy chain bind to AP2, clathrin interact through their light chains to form a cage
what GRK is in the retinaGRK1&7
what GRK ubiquitousGRK2,3,5&6
What GRK is in the testes & brainGRK4
What b-arrestin is in retinavisual & cone arrestin
What b-arrestin is ubiquitousb-arrestin 1&2
B-arrestin regulate signalling in (through signalling scaffolds)MAPK, tyrosine kinase, Src, Akt, PI 3Kinase, NFkappaB
B-arrestin plays important role incell migration, cell survivial (Akt), cell proliferation (MAPK), cancer metastasis
For B2-AR, b-arrestin can directly bind to ____ and indirectly bind to ____directly bind to Raf and ERK, indirectly with MEK to increase ERK activation
What small G-protein helps with recycling of vesicles?Rab GTPase (Rab 11)
When GPCR and G-protein are inactive, they could be in 2 wayscan be separate entities in the PM or associated in a preformed complex
memorize

Recent badges