Orai-2 is localized on secretory granules and regulates antigen-evoked Ca²⁺ mobilization and exocytosis in mast cells

Biochem Biophys Res Commun. 2014 Aug 15;451(1):62-7. doi: 10.1016/j.bbrc.2014.07.060. Epub 2014 Jul 17.

Abstract

The increase in intracellular Ca(2+) through the Ca(2+) channel is an indispensable step for the secretion of inflammatory mediators by mast cells. It was recently reported that Orai-1 is responsible for the Ca(2+) influx that is activated by depletion of stored Ca(2+). There are three isoforms of Orai: Orai-1, Orai-2, and Orai-3; however, isoforms other than Orai-1 are poorly understood. We found that Orai-2 is expressed and localized on secretory granules in RBL-2H3. Ca(2+) release from Ca(2+) store, induced by antigen stimulation, was significantly attenuated by knockdown of Orai-2, while that induced by thapsigargin was not affected. Furthermore, exocytotic release induced by antigen stimulation was inhibited in knockdown cells. This observation suggests a new role of Orai isoforms in secretory cells.

Keywords: Allergy; Mast cell; Orai; Secretory granule; Store-operated Ca channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cell Line
  • Exocytosis* / genetics
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Mast Cells / cytology
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Membrane Proteins
  • ORAI1 Protein
  • Rats
  • Secretory Vesicles / metabolism

Substances

  • Calcium Channels
  • Membrane Proteins
  • ORAI1 Protein
  • Orai1 protein, rat
  • Orai3 protein, rat
  • Calcium