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The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation

The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation

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Authors

  • Christopher M. Henstridge
  • Nariman A. B. Balenga
  • Lesley A. Ford
  • Ruth A. Ross
  • Maria Waldhoer
  • Andrew J. Irving

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Original languageEnglish
Pages183-193
Number of pages11
JournalFASEB Journal
Journal publication date2009
Volume23
Issue1
DOIs
StatePublished

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 Ca2+ release pathway, which is dependent on G alpha 13 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 CB1 antagonist AM251 evoked GPR55-mediated Ca2+ 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.-Henstridge, C. M., Balenga, N. A. B., Ford, L. A., Ross, R. A., Waldhoer, M., Irving, A. J. The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA- dependent Ca2+ signaling and NFAT activation. FASEB J. 23, 183-193 (2009)

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