2013 Fiscal Year Final Research Report

Analysis of Ca channel localized on secretory granules by lipid bilayer that mimics exocytotic sites

Research Project

Project/Area Number	23590048
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Physical pharmacy
Research Institution	Nagoya City University
Principal Investigator	HIRASHIMA Naohide 名古屋市立大学, 薬学研究科(研究院), 教授 (10192296)
Project Period (FY)	2011 – 2013
Keywords	アレルギー / カルシウムチャネル / マスト細胞 / エクソサイトーシス
Research Abstract	Mast cells play an essential role in allergic responses by secreting inflammatory mediators. The exocytotic secretion of these mediators (degranulation) is triggered by the increase in intracellular Ca2+ concentration. The main pathway for the entry of extracellular Ca2+ across the plasma membrane is store-operated Ca2+ entry through Ca2+ release-activated calcium (CRAC) channels. For Orai, one of CRAC channels,there are three isoforms, Orai, Orai-1, -2 and -3. Orai-1 is responsible for degranulation in mast cells. We found that Orai-2 was mostly localized on secretory granules, while Orai-1 and -3 were localized on the plasma membrane in mast cells. When Orai-2 was knocked down, Ca2+ release from Ca2+ store was significantly attenuated but that induced by thapsigargin was not affected. When cells were stimulated with antigen, degranulation was significantly inhibited in knockdown cells. These results suggest that Orai-2 regulates degranulation through Ca2+ release from Ca2+ store.

(3 results)