| Project/Area Number |
23247021
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SORIMACHI Hiroyuki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 分野長 (10211327)
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| Co-Investigator(Renkei-kenkyūsha) |
ONO Yasuko 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (20392376)
HATA Shoji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (10392375)
MATSUOKA Kunie 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40291158)
TONAMI Kazuo 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究員 (70511393)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2013: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2012: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
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| Keywords | カルパイン / プロテオリシス / 質量分析 / 筋ジストロフィー / 胃腸疾患 / 自己消化 / 酵素学 / 基質特異性 / 組織特異的発現 / 遺伝子改変マウス |
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| Outline of Final Research Achievements |
Calpains (CAPNs) are intracellular proteases that modulate substrate proteins by limited proteolysis. Although CAPN1/2 have well been studied so far, their physiological functions are still elusive because of their ubiquitous expression profiles.We have identified several tissue-specific calpains, and analyzed their functions in relation to the functions of the tissues where they are expressed. As a result, we revealed that defects of CAPN3 proteolytic activity cause muscular dystrophy, and that deficiencies of CAPN8/9 result in stress-induced gastric ulcer. Furthermore, other tissue-specific calpains were analyzed in terms of tissue functions. Proteomic analysis suggested that several novel substrates of these new members of calpains play important roles on pathophysiology of calpain-deficient diseases, "calpainopathies".
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