Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Henstridge, CM; Balenga, NA; Ford, LA; Ross, RA; Waldhoer, M; Irving, AJ.
The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation.
FASEB J. 2009; 23(1): 183-193. Doi: 10.1096/fj.08-108670 [OPEN ACCESS]
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Leading authors Med Uni Graz

Waldhoer Maria

Co-authors Med Uni Graz

Aghaei Bandbon Balenga Nariman

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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.

Find related publications in this database (using NLM MeSH Indexing)

Calcium Signaling - physiology

Cell Line -

GTP-Binding Protein alpha Subunits, G12-G13 - genetics

Gene Expression Regulation -

Humans -

Lysophospholipids - pharmacology

NFATC Transcription Factors - metabolism

Protein Transport -

Receptors, G-Protein-Coupled - metabolism

rhoA GTP-Binding Protein - genetics

Find related publications in this database (Keywords)

GPCR

cannabinoid

LPI

AM251

transcription

ROCK

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