Week 6 - G Protein Coupled Receptors

Question 1

How can GPCRs be turned off?

Answer 1

• persistent stimulation
• can lead to reduced ability for stimulation
• called desensitisation
• sequestration by endocytosis
• can be recycled
• down-regulated by lysosomes
• inactivation by blocking downstream signalling

Question 2

What are the two types of GPCR desensitisation?

Answer 2

homologous
- agonist specific
- agonist-induced activation
- same receptor
heterologous
- activation of different receptor
- or pathway

Question 3

How does homologous desensitisation occur?

Answer 3

• GPCR with agonist
• phosphorylated by GRK
• β-arrestin binds to phosphorylated GPCR
• an adaptor that recruits molecules for degradation

Question 4

How does heterologous desensitisation occur?

Answer 4

• second messenger kinase activated
• PKA and PKC uncouple other receptors from their G-proteins
• negative feedback loop

Question 5

What is a biased agonist?

Answer 5

• stabilises active conformation of a receptor
• stimulating some responses
• but not others
• biased towards a particular G-protein or β-arrestin
• receptors can also be biased