title: Orai-2 is localized on secretory granules and regulates antigen-evoked Ca²⁺ mobilization and exocytosis in mast cells.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ikeya
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamanoue
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mochizuki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tadokoro
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: hirashim@phar.nagoya-cu.ac.jp.
authors.forename: Naohide
authors.initials: N
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005089:Exocytosis / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins; D000071740:ORAI1 Protein; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; C573659:Orai3 protein, rat; D002118:Calcium
keywords: Allergy; Mast cell; Orai; Secretory granule; Store-operated Ca channel