Lecture 2 - G-Protein Coupled Receptor Transduction

What is the main function of a GPCR?

receive an extracellular signal and relay it into the cell using a g protein

What does GPCR stand for?

g protein coupled receptor

What are the three main classes of cell-surface receptors?

gpcrs, receptor tyrosine kinases, ligand gated ion channels

How many times does a GPCR cross the plasma membrane?

7

Where are the N-terminus and C-terminus of a GPCR located?

n terminus outside cell, c terminus inside cell

What is a conformational change?

change in shape of protein

What happens when a ligand binds to a GPCR?

receptor changes shape and activates a g protein

What is the function of a G protein?

relay signals from an activated gpcr to effector proteins inside the cell

What are the three subunits of a heterotrimeric G protein?

alpha, beta, gamma

Which G protein subunit binds GDP and GTP?

alpha subunit

What makes a G protein inactive?

gdp bound to alpha subunit

What makes a G protein active?

gtp bound to the alpha subunit

What happens when a GPCR activates a G protein?

gdp replaced by gtp

What happens to the G protein when GTP binds?

alpha unit separates from beta gamma dimer

How does a G protein switch off?

alpha subunit hydrolyses gtp into gdp and inorganic phosphate

What happens after GTP is hydrolysed?

alpha subunit reassociates with beta gammer dimer

What are the three main families of G proteins?

gs, gi, gq

What does Gs do?

activates adenylate cyclase, increasing camp production

What does Gi do?

inhibits adenylate cyclase, decreasing camp production

What does Gq do?

activates phospholipase c

What is the primary effector of Gs and Gi?

adenylate cyclase

What does adenylate cyclase do?

convert atp into camp

What is cAMP?

second messenger that carries signal inside a cell

What does cAMP activate?

protein kinase a

What happens when PKA is activated?

phosphorylates downstream proteins to produce a cellular response

What is the difference between Gs and Gi?

gs increases adenylate cyclase activity and camp, gi decreases both

What is signal amplification?

one initial signal activates many molecules, producing larger response

Why is signal amplification important?

small amount can produce a large response

What is an example of signal amplification in GPCR signalling?

epinephrine signalling causes glycogen breakdown, producing many glucose-1-phosphate molecules

What is the primary effector of Gq?

phospholipase c

What does PLC do?

splits pip2 into dag and ip3

What are the two second messengers produced when PLC splits PIP₂?

dag and ip3

What does IP₃ do?

causes calcium to be released from er

Where does DAG remain after PIP₂ is split?

plasma membrane

What activates protein kinase C (PKC)?

dag and calcium

What does PKC do?

phosphorylates downstream proteins to produce a cellular response

What is the pathway for Gs?

gpcr, gs, adenylate cyclase, increased camp, pka

What is the pathway for Gi?

gpcr, gi, inhibits adenylate cyclase, decreased camp and pka

What is the pathway for Gq?

gpcr, gq, plc, pip2, dag and ip3, calcium, pkc