| Project/Area Number |
13142210
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
WAKABAYASHI Shigeo National Cardiovascular Center Research Institute, Dept. Molecular Physiology, Director, 循環分子生理部, 部長 (70158583)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Yuko National Cardiovascular Center Research Institute, Dept. Molecular Physiology, Senior Investigator, 循環分子生理部, 室長 (80171908)
NISHITANI Tomoe National Cardiovascular Center Research Institute, Dept. Molecular Physiology, Senior Investigator, 循環分子生理部, 室長 (50393244)
HISAMITSU Takashi National Cardiovascular Center Research Institute, Dept. Molecular Physiology, Investigator, 循環分子生理部, 室員 (50327946)
IWAMOTO Takahiro 福岡大学, 医学部, 講師 (20300973)
SHIGEKAWA Munekazu National Cardiovascular Center Research Institute, Dept. Molecular Physiology, Director, 循環分子生理部, 部長 (00113738)
パン テンシャン 国立循環器病センター研究所, 循環分子生理部, 外国人特別研究員
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥74,500,000 (Direct Cost: ¥74,500,000)
Fiscal Year 2005: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2004: ¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2003: ¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2002: ¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2001: ¥16,200,000 (Direct Cost: ¥16,200,000)
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| Keywords | Na+ / H+ antiporter / Intracellular pH / Crystal structure / Biochemistry / Biophysics / nanomachine / Biological Molecule / Protein / 蛋白質 |
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| Research Abstract |
We have studied about structure, function and regulation of the Na^-/II^+ oxchanger (NHE, SLC9 family), in terms of i) mechanism of ion transport and pH-sensing, structure-function of regulatory cofactor CHP and involvement of NHE and its related proteins in diseases. (1)Mechanism of ion transport and pH-sensing. We elucidated the existence of "Wregulatory sites" in NHE1-NHE3 by measuring the reverse mode of exchange (^<22>Na^+-efllux) and identified several critical residues in NHE1 to regulate such H+-sites. We also identified the critical region regulating volume-sensing, and recently found that dimerization may be essential for the physiological activity of NHE. (2)Structure-function of CHP. We found that CHP is an essential cofactor for the plasma membrane exchangers (NHE1-3) to support the physiological activity and the second isoform CHP2 may be involved in maintenance of high pHi in cancer cells. Recently, we solved the crystal structure of CHP2 complexed with the NHE1-fragment and discovered the molecular mechanism for tight association between CHP/NHE. (3)Involvement of NHE or its related proteins in diseases. We found that in hypertrophied cardiac muscles the Na^-/Ca^<2+> exchanger is inhibited by calcineurin which is a major signaling molecule which leads to cardiac hypertrophy.
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