RT Journal Article SR Electronic T1 Segregation of Family A G Protein–Coupled Receptor Protomers in the Plasma Membrane JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 346 OP 352 DO 10.1124/mol.113.086868 VO 84 IS 3 A1 Anthony Gavalas A1 Tien-Hung Lan A1 Qiuju Liu A1 Ivan R. Corrêa, Jr. A1 Jonathan A. Javitch A1 Nevin A. Lambert YR 2013 UL http://molpharm.aspetjournals.org/content/84/3/346.abstract AB 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.