G q/11 -dependent regulation of endosomal cAMP generation by parathyroid hormone class B GPCR - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2020

G q/11 -dependent regulation of endosomal cAMP generation by parathyroid hormone class B GPCR

Résumé

cAMP production upon activation of Gsby G protein-coupled receptors has classically been considered to be plasma membrane-delimited, but a shift in this paradigm has occurred in recent years with the identification of several receptors that continue to signal from early endosomes after internalization. The molecular mech-anisms regulating this aspect of signaling remain incompletely understood. Here, we investigated the role of Gq/11 activation by the parathyroid hormone (PTH) type 1 receptor (PTHR) in mediating endosomal cAMP responses. Inhibition of Gq/11signaling by FR900359 markedly reduced the duration of PTH-induced cAMP production, and this effect was mimicked in cells lacking endogenous Gαq/11. We determined that modulation of cAMP generation by Gq/11 occurs at the level of the heterotrimeric G protein via liberation of cellsurface Gβγ subunits, which, in turn, act in a phosphoinositide-3kinase-dependent manner to promote the assembly of PTHR–βarrestin–Gβγsignaling complexes that mediate endosomal cAMP responses. These results unveil insights into the spatiotemporal reg-ulation of Gs-dependent cAMP signaling

Dates et versions

hal-03117167 , version 1 (20-01-2021)

Identifiants

Citer

Alex White, Frédéric Jean-Alphonse, Fei Fang, Karina Pena, Shi Liu, et al.. G q/11 -dependent regulation of endosomal cAMP generation by parathyroid hormone class B GPCR. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (13), pp.7455-7460. ⟨10.1073/pnas.1918158117⟩. ⟨hal-03117167⟩
65 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More