Splice Variants of GPCRs

  1. Kenneth P. Minneman
  1. Department of Pharmacology Emory University Medical School Atlanta, GA 30322
  1. E-mail kminneman{at}pharm.emory.edu; fax (404) 727-0365


Gprotein–coupled receptors (GPCRs) are encoded by a vast gene superfamily, reflecting the large number of ligands that must be specifically recognized at any given cell surface. The discovery that the variety of GPCRs is further expanded through the generation of splice variants was therefore somewhat surprising. Studies of the functional consequences of alternative splicing have focused on ligand binding, signaling, constitutive activity, and downregulation. However, GPCRs also appear to interact directly with many other intracellular proteins in addition to G proteins. Intriguingly, the domains involved in these interactions are the predominant sites of variation arising through splicing.

Graphic Each of the cultured human cells shown above expresses the dopamine D3 receptor, a G protein–coupled receptor, that has been manipulated so as to fluoresce red. Some of the cells additionally express a truncated variant of the D3 receptor (green) that prevents trafficking of both variants to the plasma membrane and that has been associated with schizophrenia. As discussed in the accompanying article, other GPCRs are subject to less drastic forms of splicing that may play important roles in their localization, trafficking, and signaling.

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