β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR.

ABSTRACT: Many G protein-coupled receptors (GPCRs) initiate a second phase of stimulatory heterotrimeric G protein (G_s)-coupled cAMP signaling after endocytosis. The prevailing current view is that the endosomal signal is inherently β-arrestin-dependent because β-arrestin is necessary for receptor internalization and, for some GPCRs, to prolong the endosomal signal. Here we revise this view by showing that the vasoactive intestinal peptide receptor 1 (VIPR1), a secretin-family polypeptide hormone receptor, does not require β-arrestin to internalize or to generate an endosomal signal. β-Arrestin instead resolves the plasma membrane and endosomal signaling phases into sequential cAMP peaks by desensitizing the plasma membrane phase without affecting the endosomal phase. This appears to occu

SUBMITTER: Blythe EE 

PROVIDER: S-EPMC10907292 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature