Gβγ translocation to the Golgi apparatus activates ARF1 to spatiotemporally regulate G protein-coupled receptor signaling to MAPK.

ABSTRACT: After activation of G protein-coupled receptors, G protein βγ dimers may translocate from the plasma membrane to the Golgi apparatus (GA). We recently report that this translocation activates extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) via PI3Kγ; however, how Gβγ-PI3Kγ activates the ERK1/2 pathway is unclear. Here, we demonstrate that chemokine receptor CXCR4 activates ADP-ribosylation factor 1 (ARF1), a small GTPase important for vesicle-mediated membrane trafficking. This activation is blocked by CRISPR-Cas9-mediated knockout of the GA-translocating Gγ9 subunit. Inducible targeting of different Gβγ dimers to the GA can directly activate ARF1. CXCR4 activation and constitutive Gβγ recruitment to the GA also enhance ARF1 translocation to the GA. We further demonstrate t

SUBMITTER: Khater M 

PROVIDER: S-EPMC8215300 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature