Abstract
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.
Footnotes
- Received April 16, 2013.
- Accepted June 13, 2013.
This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants GM078319 and GM096762]; the National Institutes of Health National Institute on Drug Abuse [Grant DA022413]; and the National Institutes of Health National Institute of Mental Health [Grant MH54137].
↵This article has supplemental material available at molpharm.aspetjournals.org.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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