G protein linked receptor signalling

Question 1

What kind of molecules do receptors on the plasma membrane bind

Answer 1

Hydrophilic

Question 2

What is the largest family of cell surface receptors?

And what processes do these receptors mediate?

Answer 2

G proteins

Metabolism, learning, memory, olfaction, vision

Question 3

What is the common structure of the 7 transmembrane passes?

Answer 3

Extracellular ligand binding domain, intracellular G protein binding domain

Question 4

What is the first messanger?

Answer 4

The ligand for the receptor

Question 5

Describe G protein linked receptors

Answer 5

7 transmembrane helices H1 -> H7

Not every transmembrane receptor is coupled to a G protein, but all G proteins bind to 7 transmembrane receptors

Question 6

What is the second messanger?

Answer 6

Molecule produced inside a cell in response to activation

Question 7

Adrenaline and G protein receptors

Answer 7

Adrenaline binds to the beta-adrenergic receptor. The beta-adrenergic receptor is coupled to a G protein which consists of 3 domains: alpha, beta and gamma. Beta and gamma never separate and are always bound.
The alpha subunit can separate from the beta, gamma pair.
The alpha subunit can bind to guanine nucleotide (GDP or GTP)
The alpha and gamma subunits are attached to the plasma membrane.

Question 8

Activating the G protein of a beta-adrenergic receptor

Answer 8

7-TM is activated and permits the exchange of GTP for GDP activating the G protein. The alpha subunit leaves the binding pair and goes off to activate other molecules (adenyl cyclase)

Question 9

G protein activation cycle (6 steps)

Answer 9

1. Binding of hormone induces a conformational change in the receptor
2. Activated receptor binds G-alpha subunit
3. Activated receptor causes conformational change in G-alpha triggering dissociation of GDP
4. Binding of GTP to G-alpha triggers dissociation of G-alpha from the receptor and G-beta-gamma
5. The hormone dissociates from the receptor. G-alpha binds to effector activating it
6. Hydrolysis of GTP to GDP causes G-alpha to dissociate from the effector and associate back with the G protein complex.

Question 10

Why is the G protein heterotrimeric?

Answer 10

Has 3 subunits

Question 11

Describe the off state of the G protein

Answer 11

Inactive, heterotrimeric (alpha, beta, gamma)

alpha subunit bound to GDP

Question 12

Cell signalling in the ovary

Answer 12

Luteinising hormone

Progesterone secretion

Question 13

Cell signalling in the muscle

Answer 13

Adrenaline

Glycogen break down

Question 14

Cell signalling in the kidney

Answer 14

Vasopressin

Water re-absorption

Question 15

What synthesises cAMP

Answer 15

Enzyme adenyl cyclase converts ATP to cAMP

Question 16

What degrades cAMP?

Answer 16

cAMP phosphodiesterase

Question 17

Provide an example of a secondary messenger

Answer 17

cAMP

Question 18

What is adenyl cyclase regulated by?

Answer 18

G proteins
G-beta-gamma
Ca2+

Question 19

What is the effect of hormones on adenyl cyclase receptors?

Answer 19

stimulate- epinephrine - receptor coupled to G-alpha-S

inhibit - adenosine - receptor coupled to G-alpha-i

Question 20

What does cAMP activate?

Answer 20

cAMP-dependent protein kinase (PKA)

EPAC

Question 21

Are there more molecules of cAMP than starting hormone?

Answer 21

Yes

Question 22

PKA structure

Answer 22

Heterotetramer

Question 23

Explain the process that leads to the release of active catalytic subunits of PKA

Answer 23

Inactive PKA is a heterotetramer of 2 regulatory subunits and 2 catalytic subunits. cAMP binds to the regulatory subunits inducing a conformational change allowing the release of active catalytic subunits.

Question 24

Cellular function dependent on IP3: Pancreas, Skeletal muscle, blood platelets

Answer 24

Pancreas = acetylcholine = amylase secretion
Skeletal muscle = acetylcholine = contraction
Blood platelets = Thrombin = Aggregation