Complementary biosensors reveal different G-protein signaling modes triggered by GPCRs and non-receptor activators

eLife

Mikel Garcia-Marcos¹ 

[1] Department of Biochemistry, Boston University School of Medicine, Boston, United States;

关键词: G-protein-coupled receptor (GPCR);    GTPase;    GEF;    BRET;    GIV;    Girdin;    Human;   

DOI  :  10.7554/eLife.65620

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY