| Popis: |
The ability of GPCRs to initiate a second phase of G protein-coupled signaling after endocytosis is now well established. The prevailing current view is that GPCR signaling from endosomes is strictly dependent on β-arrestin. Here we revise this view by demonstrating that the vasoactive intestinal peptide receptor 1 (VIPR1), a family B GPCR, is able to internalize and initiate a distinct endosomal cAMP response in cells that completely lack β-arrestin. However, VIPR1 robustly recruits β-arrestin to both the plasma membrane and endosomes, and we show that β-arrestin recruitment plays a different role in temporally resolving plasma membrane and endosomal signaling phases into separate cAMP peaks. These results delineate a third endosomal GPCR signaling mode, distinguished by not requiring β-arrestin for its production, and reveal a discrete function of β-arrestin in sculpting the spatiotemporal cAMP response. |
