Open AccessComplementary biosensors reveal different G-protein signaling modes triggered by GPCRs and non-receptor activators
Author(s) -
Mikel GarciaMarcos
Publication year - 2021
Publication title -
elife
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.879
H-Index - 139
ISSN - 2050-084X
DOI - 10.7554/elife.65620
Subject(s) - heterotrimeric g protein , g protein coupled receptor , g protein , guanine nucleotide exchange factor , microbiology and biotechnology , biology , signal transduction , gtpase activating protein , receptor , g protein coupled receptor kinase , effector , gtp binding protein regulators , biochemistry
It has become evident that activation of heterotrimeric G-proteins by cytoplasmic proteins that are not G-protein-coupled receptors (GPCRs) plays a role in physiology and disease. Despite sharing the same biochemical guanine nucleotide exchange factor (GEF) activity as GPCRs in vitro, the mechanisms by which these cytoplasmic proteins trigger G-protein-dependent signaling in cells have not been elucidated. Heterotrimeric G-proteins can give rise to two active signaling species, Gα-GTP and dissociated Gβγ, with different downstream effectors, but how non-receptor GEFs affect the levels of these two species in cells is not known. Here, a systematic comparison of GPCRs and three unrelated non-receptor proteins with GEF activity in vitro (GIV/Girdin, AGS1/Dexras1, and Ric-8A) revealed high divergence in their contribution to generating Gα-GTP and free Gβγ in cells directly measured with live-cell biosensors. These findings demonstrate fundamental differences in how receptor and non-receptor G-protein activators promote signaling in cells despite sharing similar biochemical activities in vitro.