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Gavalas, A.* ; Lan, T.H.* ; Liu, Q.* ; Corrêa, I.R.* ; Javitch, J.A.* ; Lambert, N.A.*

Segregation of family A G protein-coupled receptor protomers in the plasma membrane.

Mol. Pharmacol. 84, 346-352 (2013)
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G protein-coupled receptors (GPCRs) transduce many important physiological signals and are targets for a large fraction of therapeutic drugs. Members of the largest family of GPCRs (family A) are thought to self-associate as dimers and higher-order oligomers, although the significance of such quaternary structures for signaling or receptor trafficking is known for only a few examples. One outstanding question is the physical stability of family A oligomers in cell membranes. Stable oligomers would be expected to move through cellular compartments and membrane domains as intact groups of protomers. Here, we test this prediction by recruiting subsets of affinity-tagged family A protomers into artificial microdomains on the surface of living cells and asking if untagged protomers move into these domains (are corecruited) at the same time. We find that tagged β₂ adrenergic and μ-opioid protomers are unable to corecruit untagged protomers into microdomains. In contrast, tagged metabotropic glutamate receptor protomers do corecruit untagged protomers into such microdomains, which is consistent with the known covalent mechanism whereby these family C receptors dimerize. These observations suggest that interactions between these family A protomers are too weak to directly influence subcellular location, and that mechanisms that move these receptors between subcellular compartments and domains must operate on individual protomers.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0026-895x
e-ISSN 1521-0111
Quellenangaben Volume: 84, Issue: 3, Pages: 346-352 Article Number: , Supplement: ,
Publisher American Society for Pharmacology and Experimental Therapeutics (ASPET)
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)