2003 Fiscal Year Final Research Report Summary
The Na+/H+ exchanger as a proton regulatory system : its molecular structure and transport mechanism
| Project/Area Number |
14580664
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | National Cardiovascular Center Research Institute |
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Principal Investigator |
WAKABAYASHI Shigeo National Cardiovascular Center Research Institute, Dept.of Molecular Physiology, Director, 循環分子生理部, 部長 (70158583)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Na^+ / H^+ antiporter / Intracellular pH / Protein Crystal structure / Bioengineering / Biophysics / Nano-machine / Bio-molecule / Protein |
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| Research Abstract |
The Na^+/H^+ exchanger (NHEs, SLC9 family) are electroneutral transporters that catalyze the exchange of Na^+ and H^+ in plasma membranes or other intracellular organellar membranes in various animal species. We discovered that calcineurin B homologous protein (CHP, its ubiquitous isoform CHP1) functions as an essential cofactor to support the physiological activity by interacting with the juxtamembrane domain of the plasma membrane-type exchanger isoforms NHE1-5. Furthermore, another isoform CHP2 becomes expressed when cells are malignantly transformed and plays a role in maintaining high intracellular pH in cancer cells. We also analyzed the role of Ca^<2+>-binding sites of CHP and concluded that two Ca^<2+> ions remain to be bound to EF-hand binding sites of CHP when interacts with NHE1 in cell membranes and play an important role in maintaining the physiological function of NHE1.
In addition to H^+-transport site, H^+-regulatory site have been recognized to be important for pH regulation by NHE1. We discovered such additional H^+-binding sites in NHE1 by measuring the reverse mode reaction of NHE1 (^<22>Na^+ efflux from the cells). We also identified critical amino acid residues (Arg440, Gly455, Gly456) in NHE1 important for regulation of pH-sensor.
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Research Products
(17 results)
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[Publications] Hirata, T., Kaneko, T., Ono, T., Nakazato, T., Furukawa, N., Hasegawa, S., Wakabayashi, S., Shigekawa, M., Chang, M.-H., Romero M., Hirose, S.: "Mechanism of acid adaptation of a fish living in a pH 3.5 lake."Am J Physiol Regul Integr Comp Physiol.. 284(5). R1199-R1212 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Wakabayashi, S., Pang, T., Hisamitsu, T., Shigekawa, M.: "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.)"Kluwer Academic Publishers. 35-49 (2003)
Description
「研究成果報告書概要(欧文)」より
