regulation of PP1 (PP1c) in MUSCLE

Question 1

pp one c is controlled by…?

Answer 1

controlled by +/- Pi of Gm subunit at ser 48 and ser 67. Both +Pi by PKA in response to epinephrine.

ONLY Ser 48 is +Pi by CaMKII (diff Ca2+-CaM)

Question 2

Why epinephrine response

Answer 2

Epi tells you that you need more E in fight or flight, so want muscle involved.

Question 3

Why Ca2+ response?

Answer 3

Ca2+ in muscle = you are moving muscles… transient ca changes.

Question 4

Why +2Pi vs +1Pi

Answer 4

magnitude of response, want to be able to gradient.
When +2Pi occurs on the complex with Gm, glycogen will release PP1c into cytoplasm, which BANISHES it, so cannot interact with anything on the particle. Which means, it will not -Pi so the activity of the complex will continue.

So PP1c is inhibited by PPi1 (inhibitor).

Question 5

inhibitor bound in pp1c groove

Answer 5

PPi-1 is +Pi by PKA, so it becomes active and binds in pp1c same groove with green structure, , inhibitor stuck here, has a modest binding constant.
This means it doesnt bind bad or good, somewhere in the middle. So when inhibitor is present, it works okay but not amazing. So this tells us not ALL pp1c in cyto is inhibited by ppi-1, only some.

Question 6

states of the diagram

Answer 6

only need to understand I and E but P and D also exist.

Question 7

+Pi of ser 48

Answer 7

done by PKA, causes quick +Pi by PKA again (cooperative idea), which causes a large decrease in binding affinity of Gm (unit in muscle of pp1 complex that causes complex to be stuck to glycogen branch).

So if there is a decrease in binding affinity, there is a shift in equilibrium towards E. Which means pp1c is released, in cytosol and ppi-1 will bind to it with modest binding affinity. So if +Pi on Gm, will probably do it 2x which causes no pp1c to be bound.

Question 8

I state

Answer 8

favored when insulin present, no Pi at ser48/67

Question 9

E state

Answer 9

favored by epinephrine