Transient receptor potential ankyrin-1 (TRPA1) modulates store-operated Ca(2+) entry by regulation of STIM1-Orai1 association

Biochim Biophys Acta. 2013 Dec;1833(12):3025-3034. doi: 10.1016/j.bbamcr.2013.08.014. Epub 2013 Aug 28.


TRPA1 is a non-selective Ca(2+) permeable channel located in the plasma membrane that functions as a cellular sensor detecting mechanical, chemical and thermal stimuli, being a component of neuronal, epithelial, blood and smooth muscle tissues. TRPA1 has been shown to influence a broad range of physiological processes that involve Ca(2+)-dependent signaling pathways. Here we report that TRPA1 is expressed in MEG01 but not in platelets at the protein level. MEG01 cells maturation induced by PMA results in attenuation of TRPA1 protein expression and enhances thapsigargin-evoked Ca(2+) entry without altering the release of Ca(2+) from intracellular stores. Inhibition of TRPA1 by HC-030031 results in enhancement of both thrombin- and thapsigargin-stimulated Ca(2+) entry. Co-immunoprecipitation experiments revealed that TRPA1 associates with STIM1, as well as Orai1, TRPC1 and TRPC6. Downregulation of TRPA1 expression by MEG01 maturation, as well as pharmacological inhibition of TRPA1 by HC-030031, results in enhancement of the association between STIM1 and Orai1. Altogether, these findings provide evidence for a new and interesting function of TRPA1 in cellular function associated to the regulation of agonist-induced Ca(2+) entry by the modulation of STIM1/Orai1 interaction.

Keywords: Ca(2+) entry; MEG01 cell; Orai1; STIM1; TRP channel; TRPA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Blood Platelets / cytology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line
  • Humans
  • Isothiocyanates / pharmacology
  • Megakaryocytes / cytology
  • Megakaryocytes / drug effects
  • Megakaryocytes / metabolism
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • ORAI1 Protein
  • Protein Binding / drug effects
  • Purines / pharmacology
  • Stromal Interaction Molecule 1
  • TRPA1 Cation Channel
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thapsigargin / pharmacology
  • Thrombin / pharmacology
  • Transient Receptor Potential Channels / metabolism*
  • rap GTP-Binding Proteins / metabolism


  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Calcium Channels
  • Isothiocyanates
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • Purines
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • 2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate
  • Thapsigargin
  • Thrombin
  • RAP1B protein, human
  • rap GTP-Binding Proteins
  • Tetradecanoylphorbol Acetate
  • Calcium