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Internalization dissociates β2-adrenergic receptors
Tien-Hung Lan1, Sudhakiranmayi Kuravi, Nevin A Lambert
1Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia, United States of America.
Plos One
|March 3, 2011
Summary
G protein-coupled receptors (GPCRs) can dissociate during agonist-induced internalization. This study shows that beta-2 adrenergic receptors (β(2)ARs) break apart during cellular uptake, challenging previous assumptions about receptor stability.
Area of Science:
- Cellular Biology
- Molecular Pharmacology
- Biochemistry
Background:
- G protein-coupled receptors (GPCRs) form dimers or oligomers in cells.
- It is generally believed that associated GPCRs remain intact during trafficking between cellular compartments.
Purpose of the Study:
- To investigate the stability of self-associating GPCRs, specifically beta-2 adrenergic receptors (β(2)ARs), during agonist-induced internalization.
- To determine if GPCR dimers or oligomers dissociate during cellular uptake.
Main Methods:
- Utilized bioluminescence resonance energy transfer (BRET) to monitor β(2)ARs movement between plasma membrane and endosomes.
- Employed BRET to assess energy transfer between labeled β(2)ARs.
- Investigated the effects of agonist activation, receptor mutations, and endocytosis inhibitors on BRET signals.
Main Results:
- Agonist activation led to decreased BRET between β(2)ARs at the plasma membrane and increased BRET with endosome markers.
- Mutations impairing agonist binding or internalization also reduced BRET between β(2)ARs.
- Dissociation occurred within 30 minutes, persisted after agonist removal, and was sensitive to endocytosis inhibitors.
Conclusions:
- β(2)ARs can dissociate during agonist-induced internalization, contradicting the notion of stable receptor complexes.
- Results suggest that β(2)ARs may associate transiently or that their dimers/oligomers are actively disrupted during internalization.
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