Diversity and specificity in the regulated endocytic membrane trafficking of G-protein-coupled receptors

Many G-protein-coupled receptors (GPCRs) an regulated by endocytosis. Pharm acological studies defining distinct processes of ligand-induced sequestrat ion and down-regulation provided early evidence for significant complexity in the endocytic membrane trafficking of GPCRs, In this review, we discuss our present understanding of the diversity and specificity of GPCR endocyti c membrane trafficking, focusing primarily on proteolytic down-regulation o f GPCRs via delivery to lysosomes. U:e discuss evidence suggesting that cer tain GPCRs can be targeted selectively to lysosomes after endocytosis by th e same membrane pathway that mediates the process of rapid sequestration, a nd we highlight recent progress in understanding a mechanism that controls the sorting of a specific GPCR between distinct membrane pathways after end ocytosis by clathrin-coated pits. (C) 2001 Elsevier Science Inc. All rights reserved.