| Project/Area Number |
17081013
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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 | The University of Tokushima |
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Principal Investigator |
MIYAMOTO Kenichi The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (70174208)
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| Co-Investigator(Kenkyū-buntansha) |
TAKETANI Yutaka 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (30263825)
TATSUMI Sawako 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80420545)
SEGAWA Hiroko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (70325257)
ITOH Mikiko 兵庫県立大学, 環境人間学部, 准教授 (50314852)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥60,600,000 (Direct Cost: ¥60,600,000)
Fiscal Year 2009: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2008: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2007: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2006: ¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | 無機リン酸 / 腎臓 / ナトリウム依存性 / 輸送体 / リン利尿因子Inorganic phosphate / Kidney / Sodium-dependent / transporter / phosphaturic factor / 膜輸送 / 分子認識 / 賢臓 / リン酸 / fibroblast growth factor 23 / マイクロドメイン / リン / 腎尿細管 / トランスポーター / エンドサイトーシス / 脂質マイクロドメイン / PTH / Ezrin |
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| Research Abstract |
The maintenance of constant circulating levels of Pi depends on the activity of the kidney. Two types of Na/Pi co-transporters (Npt2a, Npt2c) have been identified in the kidney. The abundance of Npt2a and Npt2c in the apical membrane of the renal epithelial cells is a major determinant for Pi homeostasis. Npt2a knockout (KO) mice exhibit increased urinary Pi excretion, a 50% to 70% decrease in renal BBM vesicle Na/Pi cotransport, and hypophosphatemia. Npt2a KO mice also overexpress Npt2c, which may support residual renal Pi reabsorption function. Laboratory and bone abnormalities are more profound in Npt2a^<-/->Npt2c^<-/->double knockout (DKO) mice than in animals with ablation of only one transporter (Npt2a or Npt2c), indicating that both molecules have similar non-redundant roles in Pi homeostasis in rodents and humans. In addition, we found that the mutations of human Npt2c cause hereditary hypophosphatemie rickets with hypercalciuria (ITHRH)
After correct targeting and insertion into the plasma membrane of epithelial cells, specific protein-protein interactions may be required to stabilize the final localization of membrane proteins. Classical yeast two-hybrid screens performed against the C-terminus of NaPi-ll (Npt2a and Npt2c) revealed interactions of this cotransporter with several PDZ domain containing proteins that may contribute to the stabilization of NaPi-ll at the apical membrane. NaPi-He (Npt2c) was shown to interact with NHERF1 and NHERF4. The consequences of these interactions for apical positioning and regulation of NaPi-llc remain to be clarified. In this study, we discovered new aspect of the regulation of the Pi transportsome in the kidney.
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