DHHC5-mediated palmitoylation of S1P receptor subtype 1 determines G-protein coupling.

ABSTRACT: Sphingosine 1-phosphate (S1P) is a pleiotropic lipid mediator involved in the regulation of immune cell trafficking and vascular permeability acting mainly through G-protein-coupled S1P receptors (S1PRs). However, mechanism underlying how S1PRs are coupled with G-proteins remains unknown. Here we have uncovered that palmitoylation of a prototypical subtype S1P₁R is prerequisite for subsequent inhibitory G-protein (Gi) coupling. We have identified DHHC5 as an enzyme for palmitoylation of S1P₁R. Under basal conditions, S1P₁R was functionally associated with DHHC5 in the plasma membranes (PM) and was fully palmitoylated, enabling Gi coupling. Upon stimulation, the receptor underwent internalisation leaving DHHC5 in PM, resulting in depalmitoylation of S1P

SUBMITTER: Badawy SMM 

PROVIDER: S-EPMC5707436 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature