| Project/Area Number |
09044208
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Functional biochemistry
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| Research Institution | Institute of Molecular and Cellular Biosciences, University of Tokyo |
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Principal Investigator |
SUZUKI Koichi University of Tokyo, Institute of Molecullar and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (80011948)
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| Co-Investigator(Kenkyū-buntansha) |
BECKMANN Jacques Genethon Institute, Director, 部長(研究職)
KIMURA Sumiko Chiba University, Faculty of Science, Associate Professor, 理学部, 助教授 (50093232)
SORIMACHI Hiroyuki University of Tokyo, Graduate School of Agriculture and Life, Associate Professo, 大学院・農学生命科学研究科, 助教授 (10211327)
ISHIURA Shoichi University of Tokyo, Graduate School of Arts & Sciences Professor, 大学院・総合文化研究所, 教授 (10158743)
RICHARD Isab Genethon研究所, 研究員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | calpain / connectin / muscular dystrophy / titin / protease / fodrin / p94 / カルバイン / 蛋白質分解 / 筋肉 / 筋ジストロフィー |
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| Research Abstract |
Calpain is a typical intracellular Ca-dependent protease and hydrolyzes various cellular proteins in a limited manner, changes their properties, and known as a biomodulator. p94 is a calpain homologue expressed specifically in skeletal muscle. p94 is unique in having various properties distinct from ordinary ubiquitous calpains, e.g. autolyzes very rapidly apparently in the absence of Ca2+, binds to connectin in skeletal muscle at least at two specific sites, contains a nuclear translocation signal, has three insertion sequences, hydrolyzes fodrin, calpastatin, HSP6O, etc.
Quite recently, p94 has been identified as a gene responsible for limb-girdle type 2A muscular dystrophy (LGMD2A). We selected 10 point mutants from various mutants found in LGMD2A patients and the point mutants were expressed in COS cells. Expressed p94 point mutants were examined for the unique properties listed above in order to identify which properties are directly correlated to LGMD2A.Binding to connectin and rapid autolysis showed no direct correlation to LGMD2A but a toss of proteolytic activity against fodrin, calpastatin, HSP6O resulted in LGMD2A Thus the next important issue is to identify a substrate(s) of p94 which directly or eventually activates degradation of muscle proteins and to clarify a mechanism for activation of muscle protein degradation. Studies are now in progress along this line.
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