2004B15 Describe the mechanism of action of G-proteins in the cell.

 

List:

·       Diagramme

·       G protein

·       G protein subtypes

 

Diagramme:

 

G protein:

Structure

·  Heterotrimeric ICF protein

·  α, β, γ subunits

Function

·  Transduces signal from ECF to ICF

·  Amplifies signal 100x

·  Self-inactivates

·  Unidirectional

·  Metabotropic effects

·  Cell-dependent effects

Time course

·  Onset: seconds to minutes

·  Duration: minutes

o Longer than ligand binding

o Longer than plasma half life may predict (e.g. adrenaline)

Mechanism of tolerance

·  ICF carboxyl terminal is phosphorylated

·  β-arrestin binds

·  Receptor is downregulated and destroyed

 

G protein subtypes:

Gs

·  e.g. adrenaline at β1

·  α-GTP stimulates adenylyl cyclase activity -> ↑cAMP -> ↑protein kinase activity

Gi

·  e.g. morphine at μ opioid receptor

·  α-GTP inhibits adenylyl cyclase -> ↓cAMP -> ↓protein kinase activity

Gq

·  e.g. vasopressin at V1R

·  α-GTP activates PLC

·  PLC cleaves PIP2 into IP3 and DAG

·  IP3 -> ↑ ICF [Ca2+]

·  DAG activates PKC

Small G protein

·  Same as α-subunit of heterotrimeric G proteins

·  Free in ICF

·  Hydrolyses GTP

·  Role in gene expression, cytoskeletal function etc.

 

 

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