2011 Fiscal Year Final Research Report
Molecular-targeted therapy for nephrogenic diabetes insipidus based on the trafficking mechanism of water channel
| Project/Area Number |
21591053
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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 |
Kidney internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NODA Yumi 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (30372436)
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| Project Period (FY) |
2009 – 2011
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| Keywords | アクアポリン / 尿崩症 / 腎臓集合管 / 尿濃縮 / 細胞内輸送 / アクチン / ミオシン / トロポミオシン |
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| Research Abstract |
Water channel aquaporin-2(AQP2) regulates the water reabsorption in the kidney collecting ducts, which is the key event for maintenance of body water balance. Its impairments result in various water balance disorders including diabetes insipidus, which is a disease characterized by a massive loss of water through the kidney, leading to severe dehydration in the body. We discovered AQP2 movement is directly and negatively regulated by tropomyosin-5b(TM5b). This indicates TM5b is an appropriate therapeutic target for nephrogenic diabetes insipidus. We succeeded in the specific inhibition of TM5b that rescues the trafficking defect of AQP2 mutants. Moreover, we discovered the water transport activity of individual AQP2 protein is regulated by PKA phosphorylation.
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