Allosteric modulation of GPCR-induced β-arrestin trafficking and signaling by a synthetic intrabody.

ABSTRACT: Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a primary determinant of β-arrestin (βarr) recruitment and trafficking. For several GPCRs such as the vasopressin receptor subtype 2 (V₂R), agonist-stimulation first drives the translocation of βarrs to the plasma membrane, followed by endosomal trafficking, which is generally considered to be orchestrated by multiple phosphorylation sites. We have previously shown that mutation of a single phosphorylation site in the V₂R (i.e., V₂R^T360A) results in near-complete loss of βarr translocation to endosomes despite robust recruitment to the plasma membrane, and compromised ERK1/2 activation. Here, we discover that a synthetic intrabody (Ib30), which selectively recognizes activa

SUBMITTER: Baidya M 

PROVIDER: S-EPMC9360436 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature