| Project/Area Number |
14580664
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | National Cardiovascular Center Research Institute |
|---|
Principal Investigator |
WAKABAYASHI Shigeo National Cardiovascular Center Research Institute, Dept.of Molecular Physiology, Director, 循環分子生理部, 部長 (70158583)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Na^+ / H^+ antiporter / Intracellular pH / Protein Crystal structure / Bioengineering / Biophysics / Nano-machine / Bio-molecule / Protein / Na+ / H+アンチポータ |
|---|
| 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.
|
