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G protein-coupled receptor sorting to endosomes and lysosomes. Annu Rev Pharmacol Toxicol 2008;48:601-29

Date

11/13/2007

Pubmed ID

17995450

Pubmed Central ID

PMC2869288

DOI

10.1146/annurev.pharmtox.48.113006.094646

Scopus ID

2-s2.0-41149154050   336 Citations

Abstract

The heptahelical G protein-coupled receptors (GPCRs) belong to the largest family of cell surface signaling receptors encoded in the human genome. GPCRs signal to diverse extracellular stimuli and control a vast number of physiological responses, making this receptor class the target of nearly half the drugs currently in use. In addition to rapid desensitization, receptor trafficking is crucial for the temporal and spatial control of GPCR signaling. Sorting signals present in the intracytosolic domains of GPCRs regulate trafficking through the endosomal-lysosomal system. GPCR internalization is mediated by serine and threonine phosphorylation and arrestin binding. Short, linear peptide sequences including tyrosine- and dileucine-based motifs, and PDZ ligands that are recognized by distinct endocytic adaptor proteins also mediate internalization and endosomal sorting of GPCRs. We present new data from bioinformatic searches that reveal the presence of these types of sorting signals in the cytoplasmic tails of many known GPCRs. Several recent studies also indicate that the covalent modification of GPCRs with ubiquitin serves as a signal for internalization and lysosomal sorting, expanding the diversity of mechanisms that control trafficking of mammalian GPCRs.

Author List

Marchese A, Paing MM, Temple BR, Trejo J

Author

Adriano Marchese PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Arrestins
Endosomes
Humans
Ligands
Lysosomes
Phosphorylation
Protein Sorting Signals
Receptors, G-Protein-Coupled
Ubiquitin