Ocular albinism: evidence for a defect in an intracellular signal transduction system

G protein-coupled receptors (GPCRs) participate in the most common signal t ransduction system at the plasma membrane(1). The wide distribution of hete rotrimeric C proteins in the internal membranes suggests that a similar sig nalling mechanism might also be used at intracellular locations(2). We prov ide here structural evidence that the protein product of the ocular albinis m type 1 gene (OA1). a pigment cell-specific integral membrane glycopratein (3). represents a novel member of the GPCR superfamily and demonstrate that it binds heterotrimeric G proteins. Moreover, we show that OA1 is not foun d at the plasma membrane, being instead targeted to specialized intracellul ar organelles, the melanosomes. Our data suggest that OA1 represents the fi rst example of an exclusively intracellular GPCR and support the hypothesis that GPCR-mediated signal transduction systems also operate at the interna l membranes in mamalian cells.