Internal PDZ ligands: novel endocytic recycling motifs for G protein-coupled receptors

Internalization, recycling and lysosomal sorting are key processes that regulate the temporal and spatial signaling of G protein-coupled receptors (GPCRs). Interactions between GPCR intracytosolic sorting signals and adaptor proteins facilitate trafficking through the endocytic pathway. To date only a few sorting signals and molecules that regulate GPCR trafficking have been identified. A study reported in the May 2005 issue of Molecular Pharmacology has now identified an internal PDZ ligand motif that seems to regulate efficient recycling of the ET(A) endothelin receptor. This finding now expands the diversity of GPCR sorting motifs to include internal and C-terminal PDZ ligands, tyrosine-based motifs, and lysine residues capable of being ubiquitinated.