Biological Signalling: GPCR

Question 1

What does GPCR stand for?

Answer 1

G protein coupled receptor

Question 2

Epinephrine is a derivative of _____

Answer 2

tyrosine

Question 3

What are 3 components of heterotrimeric GPCR Signalling?

Answer 3

1. plasma membrane receptor with 7 TM
2. heterotrimeric guanosine nucleotide binding protein (G-protein)
3. intracellular enzyme that generates a 2nd messenger

Question 4

What does the binding of the ligand to the beta adrenergic receptor cause?

Answer 4

• structural change on cytoplasmic side
• G alpha,beta,gamma bind the B receptor
• Gprotein is GDP bound inactive

Question 5

Gprotein bound to activated receptor causes:

Answer 5

• GDP/GTP exchange and binding affinity

- activated G protein = change shape = kick out the Ga-GTP

Question 6

Gas - GTP associates with

Answer 6

Adenylyl cyclase

Question 7

AC catalyzes the formation of

Answer 7

• ATP to form cAMP

Question 8

cAMP activates

Answer 8

PKA
protein kinase a
which phosphorylates cellular proteins that cause a cellular response to epinephrine

Question 9

Where can this beta adrenergic pathway be stopped?

Answer 9

• Gai (inactivate/inhibitory) binds and deactivates adenylyl cyclase (cant form cAMP)
• phosphodiesterase PDE breaks down cAMP to 5’AMP

Question 10

What does caffeine do to this pathway?

Answer 10

• inhibits PDE

- prevents breakdown of cAMP

Question 11

Gs bound GDP is ____

Answer 11

inactive

cannot activate AC

Question 12

Gs contact with hormone receptor (beta adrenergic receptor) causes

Answer 12

GTP displaces GDP bound to Gs

Question 13

Gs bound GTP _____

Answer 13

• dissociates into Gsa and Gsby subunits

Question 14

Active complex of Gs protein is ___

Answer 14

Gsa - GTP

- activates adenylyl cyclase

Question 15

What do Gai proteins do?

Answer 15

• inhibit the formation of second messenger

- via cytoplasmic facing enzyme AC

Question 16

What are 4 turn off mechanisms?

Answer 16

1. epinephrine dissociates
2. GTPase: timer that G-a subunit hydrolyses GTP (goes back to GDP)
3. PDE: cAMP broken down to 5’AMP
4. Internaliation of receptors beta adrenergic receptor is phosphorylated and internalized (endocytosis)

Question 17

What is the first step of internalizing the epinephrine receptor to turn off epinephrine mechanism?

Answer 17

• phosphorylation of the b adrenergic receptor

- on serine residue of C terminus

Question 18

What phosphorylates the beta adrenergic receptor?

Answer 18

bARK

- beta adrenergic receptor kinase

Question 19

bAR forms a complex with _____

Answer 19

beta arrestin bARR

Question 20

Receptor arrestin complex does what?

Answer 20

• enters the cell by endocytosis

- arrestin dissociates and receptor is dephosphorylated and then returns back to cell surface

Question 21

What other G proteins are there?

Answer 21

Gaq

Question 22

What does Gaq stimulate?

Answer 22

• PL-C enzyme (instead of AC)

- increase DAG and IP3

Question 23

What does DAG activate?

Answer 23

PKC (cell growth responses)

Question 24

What does IP3 activate?

Answer 24

Ca2+ released inside the cell for smooth muscle response and Ca2+dependent signalling

Question 25

What are two types of neurotransmitters for metabotropic receptors? (GPCR)

Answer 25

- biogenic amines | - neuropeptides

Question 26

List some biogenic amines:

Answer 26

- acetylcholine - nicotinic receptors - muscarinic receptors : Gai and Gaq - Epinephrine and norepinephrine - dopamine - serotonin

Question 27

What does M1-5 do?

Answer 27

muscarinic receptor: - stimulates Gai and Gaq - decreased HR and contraction - increased smooth muscle contraction of gut (rest and digest)

Question 28

What does epinephrine and norepinephrine do?

Answer 28

- opposite to M15 - a1 receptor activates Gaq and a2 receptor activates Gai - relax smooth muscle of gut - vasoconstriction of gut blood vessel, glucagon release - increase blood FFA and glucose - beta 1, 2, 3, (bAR) activates Gas: - increased HR and contraction - vasodilation of skeletal muscle blood vessels

Question 29

Dopamine?

Answer 29

Dopamine 1 receptors activate Gas = euphoria | Dopamine 2 receptors activate Gai = motor coordination

Question 30

How are steroid hormone receptors transported and how does it target DNA?

Answer 30

- carrier serum proteins - diffuse across PM - bind Rec (receptor protein) - conformational change of receptor protein - Rec binds HRE in DNA - regulates transcription of mRNA