Chapter One - Ubiquitination and Deubiquitination of G Protein-Coupled Receptors.

Published

Journal Article (Review)

The seven-transmembrane containing G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors. Transmembrane signaling by GPCRs is fundamental to many aspects of physiology including vision, olfaction, cardiovascular, and reproductive functions as well as pain, behavior and psychomotor responses. The duration and magnitude of signal transduction is tightly controlled by a series of coordinated trafficking events that regulate the cell-surface expression of GPCRs at the plasma membrane. Moreover, the intracellular trafficking profiles of GPCRs can correlate with the signaling efficacy and efficiency triggered by the extracellular stimuli that activate GPCRs. Of the various molecular mechanisms that impart selectivity, sensitivity and strength of transmembrane signaling, ubiquitination of the receptor protein plays an important role because it defines both trafficking and signaling properties of the activated GPCR. Ubiquitination of proteins was originally discovered in the context of lysosome-independent degradation of cytosolic proteins by the 26S proteasome; however a large body of work suggests that ubiquitination also orchestrates the downregulation of membrane proteins in the lysosomes. In the case of GPCRs, such ubiquitin-mediated lysosomal degradation engenders long-term desensitization of transmembrane signaling. To date about 40 GPCRs are known to be ubiquitinated. For many GPCRs, ubiquitination plays a major role in postendocytic trafficking and sorting to the lysosomes. This chapter will focus on the patterns and functional roles of GPCR ubiquitination, and will describe various molecular mechanisms involved in GPCR ubiquitination.

Full Text

Duke Authors

Cited Authors

  • Jean-Charles, P-Y; Snyder, JC; Shenoy, SK

Published Date

  • 2016

Published In

Volume / Issue

  • 141 /

Start / End Page

  • 1 - 55

PubMed ID

  • 27378754

Pubmed Central ID

  • 27378754

Electronic International Standard Serial Number (EISSN)

  • 1878-0814

Digital Object Identifier (DOI)

  • 10.1016/bs.pmbts.2016.05.001

Language

  • eng

Conference Location

  • Netherlands