| 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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| 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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