| Project/Area Number |
11470022
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Institute of Life Science, Kurume University (2000)
The University of Tokyo (1999) |
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Principal Investigator |
TAKESHIMA Hiroshi Institute of Life Science, Kurume University, 分子生命科学研究所, 教授 (70212024)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | ryanodine receptor / Ca^<2+> release channel / Excitation-contraction coupling / fihydropyridina receptor / Ca^<2+> sigualing / Ca^2^+放出チャネル / Ca^2^+シグナリング |
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| Research Abstract |
In excitable cells, the depolarization signal of cell-surface membrane is converted into cytoplasmic Ca^<2+> signaling using intracellular Ca^<2+> stores. The final goal of my study is to understand the molecular architecture of the signal conversion machinery, and in this project I focused on the function of the ryanodine receptor as an inracellular Ca^<2+> release channel and the molecular components of intracellular Ca^<2+> stores. In experiments on the ryanodine receptor, a Ca^<2+>-binding site for channel inactivation has been mapped on the primary structure, and co-existence of ryanodine receptor subtypes in the triad junction has been defined in skeletal muscle cells. On the other hands, novel membrane proteins namely mitsugumins have been identified currently. Mitsugumin29 is a novel member of the syanptophisin family bearing 4 transmembrane segments. When skeletal muscle cells lacked mitsugumin29, triad junctions could not be constructed correctly and thus efficiency of excitation-contraction coupling reduced. Junctophilin (mitsugumin72) is composed of the cytoplasmic region recognizing the cell-surface membrane and the transmembrane segment spanning the Ca^<2+> store membrane. When cardiac muscle lacked junctophilin, junctional membrane structures between the cell-surface membrane and Ca^<2+> store were poorly developed and resulting abnormal Ca^<2+> signaling resulted in heart failure during embryonic stages.
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