Figure 5: Model for Gαs regulation of GPCR endosomal sorting.
From: Gαs regulates the post-endocytic sorting of G protein-coupled receptors
Gαs promotes the endosomal sorting of GPCRs into the ILVs of MVBs via the ESCRT machinery. (a) Gαs interacts directly with GASP-1 and dysbindin on endosomal membranes and facilitates/stabilizes their downstream interactions with HRS and the ESCRT machinery. These interactions promote the endosomal sorting and downregulation of a subset of GPCRs, such as DOP and D2R, for which ESCRT sorting is ubiquitination independent. (b) Gαs is also required for the endosomal sorting of GPCRs, such as CXCR4, that are sorted by the ubiquitin- and HRS-mediated ESCRT machinery, but are independent of GASP-1 and dysbindin. However, the molecular components of the Gαs-regulated CXCR4 endosomal-sorting machinery have yet to be identified.
