Cell Signalling 2

Question 1

Some GPCRs exert effect via G-protein called Gq - how is that different from Gs and Gi?

Answer 1

The previous ones act on Adenylyl cyclase, while Gq activates the anzyme Phospholipase C
-> cleaves a lipid molecule from the plasma membrane = inositol phospholipid (a phospholipid with sugar inositol attached to its head)

Question 2

What kind of second messenger molecules does phospholipase C generate? What do they do?

Answer 2

1. Inositol 1,4,5 - triphosphate (IP3) = water soluable sugar phosphate
   -> once release into cytosol -> binds to Ca2+ channels of ER -> Ca2+ stored there rushes out -> higher concentration -> signaling for other proteins

2.Diacylglyserol (DAG) = lipid produced by Phospholipase C that remains embedded in the plasma membrane
-> there,it recruits and activates protein kinase to translocate them from cytosol to plasma membrane = Protein Kinase C (PKC) which needs Ca2+ to become active
-> once Ca2+ binds -> acts similar as PKA just phosphorylating different proteins

Question 3

In general, Ca2+ plays a large role in many intracellular signalling pathways - how come it is pushed into the cytosol so rapidly?

Answer 3

The concentration of Ca2+ in the cytosol is very low (in unstimulated cell) compared to extracellular space or ER
- the differences maintained by specialized pumps that force Ca2+ out of the cytosol
=> steep electrochemical gradient
-> once Ca2+ channels transiently open -> rushes into cytosol

• pumps can terminate the signal

Question 4

The effect of Ca2+ is largely indirect - what kind of protein mediator could it use?

Answer 4

Calmodulin - most commonly, present in cytosol
- once Ca2+ binds to it -> conformational change -> now, can interact with other proteinsalong the pathway
-> e.g. Ca2+/Calmodulin-dependent protein kinases (Cam-Kinases) -> phosphorylation of target proteins/molecules

E.g. neurons exert this to induce learning or memory e.g. adding AMPA receptors to the plasma membrane

Question 5

How does light get transduced in photoreceptors?

Answer 5

You can find it in structure biology :)

Question 6

What is meant by adaptation in terms of signalling pathways? What mechanism is responsible?

Answer 6

= modulation of response to extracellular signal molecules depending on their amount

• If there is little of it (e.g. dark conditions -> small amount of photons) -> cells engage in more amplification
• If there is too much (e.g. bright conditions) -> cell can decrease their amplification to not get overwhelmed
• This is achieved by positive or negative feedback loops
  
  • e.g. in photoreceptors - intense light response decreases cytosolic Ca2+ concentration -> inhibits enzymes responsible for amplification