Membrane Signalling 2

Question 1

G-Protein coupled receptors

Answer 1

All G protein coupled receptors have 7 membranes folding back and forth across spanning the membrane

Hierarchical signal cascade

G proteins can in turn regulate enzymes or ion channels

activated by neurotransmitters, hormones, local mediators

Question 2

Overview of G-protein signalling

Answer 2

• binding of first messenger to the receptor causes a change in shape of the G protein. This causes the alpha subunit to exchange GDP for GTP, this subunit then dissociates from the Beta Subunit and both can move to interact with other proteins the effectors proteins to modulate the activity of a the cell leading to their activity or inhibition.
• once the g protein alpha subunit has associated with an effector, its GTPase activity is activated and GTP is hydrolysed to GDP. This makes the subunit inactive

Question 3

GCPRS

Answer 3

These can regulate the activity of effectors such as :
- Adenylyl Cyclase
- Phospholipase C
- Ion channels

Question 4

Regulation of Adenylyl Cyclase

Answer 4

• membrane bound enzyme
• present in eukaryotic and prokaryotes
• If the G protein stimulates AC it is called Gs
• If the G protein inhibits AC it is called Gi

The signal can be terminated by the enzyme cAMP phosphodiesterase, that breaks down cAMP to AMP

Question 5

Why does coffee make you feel more awake ?

Answer 5

• active component is caffeine
• caffeine inhibits cAMP phosphodiesterase so cAMP levels remain high for longer
• increased heart rate and force of contraction
• more oxygen to brain and tissues
• increased feeling of vitality and energy.

Question 6

Regulation of phospholipase C ( PLC )

Answer 6

• the action of plc produces inositol tri-phosphate (IP3) and 1-2 -diacylglycerol (DAG) from membrane PIP2
• the receptor is linked to PLC by G proteins
• IP3 moves into cytosol and DAG remains in the membrane
• IP3 and DAG work together to activate enzymes and to increase intracellular calcium levels.

Question 7

Role of Ca2+ in cellular mechanisms

Answer 7

• ca2 binding to proteins is non covalent and causes structural changes
• can activate enzymes, ion channels and cytoskeletal proteins

Question 8

DAG / Ca2+

Answer 8

• both activate protein kinase C
• cause PKC translocation from cytoplasm to plasma membrane
• PKC phosphorylates proteins on serine and threonine residues
• PKC is important on cellular growth and division

Question 9

Regulation of ion channels

Answer 9

• an activated G protein can directly gate an ion channel
• the effect can also be indirect, where a second messenger alters the gating of an ion channel