Splice Variants of GPCRs
- E-mail kminneman{at}pharm.emory.edu; fax (404) 727-0365
Abstract
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.
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.
- © American Society for Pharmacology and Experimental Theraputics 2001
