Endo ‐lysosomal sorting of G‐protein‐coupled receptors by ubiquitin: Diverse pathways for G‐protein‐coupled receptor destruction and beyond

Ubiquitination of GPCRs and endocytic adaptor proteins facilitates GPCR trafficking to lysosomes and. In addition, ubiquitination of GPCRs and GPCR effectors can mediate the activation of specific signaling pathways. GPCR ubiquitination is also critical for targeting some GPCRs for degradation by proteasomes. This review highlights the multiple pathways by which ubiquitin controls GPCR endo ‐lysosomal sorting and signaling, which expand the function of ubiquitin in regulating GPCR biology. Ubiquitin is covalently attached to substrate proteins in the form of a single ubiquitin moiety or polyubiquitin chains and has been generally linked to protein degradation, however, distinct types of ubiquitin linkages are also used to control other critical cellular processes like cell signaling. Over forty mammalian G protein ‐coupled receptors (GPCRs) have been reported to be ubiquitinated, but despite the diverse and rich complexity of GPCR signaling, ubiquitin has been largely ascribed to receptor degradation. Indeed, GPCR ubiquitination targets the receptors for degradation by lysosome, which is mediated by the End osomal Sorting Complexes Required for Transport (ESCRT) machinery, and the proteasome. This has led to the view that ubiquitin and ESCRTs primarily function as the signal to target GPCRs for destruction. Contrary to this conventional view, studies indicate that ubiquitination of certain GPCRs and ca nonical ubiquitin‐binding ESCRTs are not required for receptor degra...

Source: Traffic - November 18, 2018 Category: Research Authors: Michael R. Dores, JoAnn Trejo Tags: REVIEW Source Type: research