Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 23 (1), 183-93

The GPR55 Ligand L-alpha-lysophosphatidylinositol Promotes RhoA-dependent Ca2+ Signaling and NFAT Activation

Affiliations

The GPR55 Ligand L-alpha-lysophosphatidylinositol Promotes RhoA-dependent Ca2+ Signaling and NFAT Activation

Christopher M Henstridge et al. FASEB J.

Abstract

The endogenous phospholipid l-alpha-lysophosphatidylinositol (LPI) was recently identified as a novel ligand for the orphan G protein-coupled receptor 55 (GPR55). In this study we define the downstream signaling pathways activated by LPI in a human embryonic kidney (HEK) 293 cell line engineered to stably express recombinant human GPR55. We find that treatment with LPI induces marked GPR55 internalization and stimulates a sustained, oscillatory Ca(2+) release pathway, which is dependent on Galpha13 and requires RhoA activation. We then establish that this signaling cascade leads to the efficient activation of NFAT (nuclear factor of activated T cells) family transcription factors and their nuclear translocation. Analysis of cannabinoid ligand activity at GPR55 revealed no clear effect of the endocannabinoids anandamide and 2-arachidonoylglycerol; however, the classical CB(1) antagonist AM251 evoked GPR55-mediated Ca(2+) signaling. Thus, LPI is a potent and efficacious ligand at GPR55, which is likely to be a key plasma membrane mediator of LPI-mediated signaling events and changes in gene expression.

Similar articles

See all similar articles

Cited by 89 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback