Analysis of Ca channel localized on secretory granules by lipid bilayer that mimics exocytotic sites
| Project/Area Number |
23590048
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
HIRASHIMA Naohide 名古屋市立大学, 薬学研究科(研究院), 教授 (10192296)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| 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 / 開口放出 / 分泌小胞 / 生物物理 |
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| 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.
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Report
(4 results)
Research Products
(23 results)
