2005 Fiscal Year Final Research Report Summary
Structure, function and regulation of the mammalian Na+/H+ antiporters
| 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)
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| Project Period (FY) |
2001 – 2005
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| Keywords | Na+ / H+ antiporter / Intracellular pH / Crystal structure / Biochemistry / Biophysics / nanomachine / Biological Molecule / Protein |
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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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[Journal Article] Novel Role of Neuronal Ca2+ Sensor 1 as a Survival Factor Up-Regulated in Injured Neurons2006
Author(s)
Nakamura, T.Y., Jeromin, A., Smith, G., Kurushima, H., Koga, H., Nakabeppu, Y., Wakabayashi, S., Nabekura, J.
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Journal Title
J. Cell Biol. 172(7)
Pages: 1081-1091
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification and characterization of GSRP-56, a novel Golgi-localized spectrin-repeat containing protein2006
Author(s)
Kobayashi, Y., Katanosaka, Y., Iwata, Y., Shigekawa, M., Wakabayashi, S.
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Journal Title
Exp. Cell Res. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Calcineurin Inhibits Na+/Ca2+ Exchange in Phenylephrine-treated Hypertrophic Cardiomyocytes2005
Author(s)
Katanosaka, Y., Iwata, Y., Kobayashi, Y., Shibasaki, F., Wakabayashi, S., Shigekawa, M.
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Journal Title
J. Biol. Chem. 280(7)
Pages: 5764-5772
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by A23187 in CEM cells2005
Author(s)
Hamahata, K., Adachi, S., Matsubara, H., Okada, M., Imai, T., Watanabe, K., Toyokuni, S., Ueno, M., Wakabayashi, S., Katanosaka, Y., Akiba, S., Kubota, M., Nakabata, T.
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Journal Title
Eur. J. Pharmacol. 516
Pages: 187-196
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protective effects of Ca2+ handling drugs against abnormal Ca2+ homeostasis and cell damage in myopathic skeletal muscle cells2005
Author(s)
Iwata, Y., Katanosaka, Y., Zhu, S., Kobayashi, Y., Hanada, H., Shigekawa, M., Wakabayashi, S.
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Journal Title
Biochem. Pharmacol. 70
Pages: 740-751
Description
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[Journal Article] Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE12005
Author(s)
Ben Ammar, Y., Takeda, S., Sugawara, M., Miyano, M., Mori, H., Wakabayashi, S.
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Journal Title
Acta Crystallographica Section F 61(10)
Pages: 956-958
Description
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[Journal Article] Association of Genetic Polymorphisms of Sodium-Calcium Exchanger 1 Gene, NCX1, with Hypertension in a Japanese General Population.2004
Author(s)
Kokubo, Kokubo, Y., Inamoto, N., Tomoike, H., Kamide, K., Takiuchi, S., Kawano, Y., Tanaka, C., Katanosaka, Y., Wakabayashi, S., Shigekawa, M., Hishikawa, 0., Miyata, T.
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Journal Title
Hypertension Res. 27(10)
Pages: 697-702
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanism of acid adaptation of a fish living in a pH 3.5 lake2003
Author(s)
Hirata, T., Kaneko, T., Ono, T., Nakazato, T., Furukawa, N., Hasegawa, S., Wakabayashi, S., Shigekawa, M., Chang, M.-H., Romero M., Hirose, S.
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Journal Title
Am J Physiol 284(5)
Pages: R1199-R1212
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel2003
Author(s)
Iwata, Y., Katanosaka, Y., Arai, Y., Komamura, K., Miyatake, K., Shigekawa, M.
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Journal Title
J. Cell Biol. 161(5)
Pages: 957-967
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two Fundamental Regulatory Factors of the Na+/H+ Exchangers; The Proton and CHP. The Sodium-Hydrogen Exchange; From Molecule to its Role in Disease (Ed. by Karmazyn, M., Avkiran, M., Fliegel, L.)2003
Author(s)
Wakabayashi, S., Pang, T., Hisamitsu, T., Shigekawa, M.
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Journal Title
Kluwer Academic Publishers 35-49
Description
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