G?s protein binds ubiquitin to regulate epidermal growth factor receptor endosomal sorting.

ABSTRACT: The G?s subunit is classically involved in the signal transduction of G protein-coupled receptors (GPCRs) at the plasma membrane. Recent evidence has revealed noncanonical roles for G?s in endosomal sorting of receptors to lysosomes. However, the mechanism of action of G?s in this sorting step is still poorly characterized. Here, we report that G?s interacts with ubiquitin to regulate the endosomal sorting of receptors for lysosomal degradation. We reveal that the N-terminal extremity of G?s contains a ubiquitin-interacting motif (UIM), a sorting element usually found in the endosomal sorting complex required for transport (ESCRT) machinery responsible for sorting ubiquitinated receptors into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs). Mutation of the UIM in G?s confirmed the importance of ubiquitin interaction for the sorting of epidermal growth factor receptor (EGFR) into ILVs for lysosomal degradation. These findings demonstrate a role for G?s as an integral component of the ubiquitin-dependent endosomal sorting machinery and highlight the dual role of G?s in receptor trafficking and signaling for the fine-tuning of the cellular response.

SUBMITTER: Li X 

PROVIDER: S-EPMC5754765 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature