Studies on the physiological roles of intracellular OLO chloride channels
| Project/Area Number |
14370316
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
UCHIDA Shinichi Tokyo Medical & Dental University, Dept. of Nephrology, 医学部附属病院, 講師 (50262184)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | CLC chloride channel / intracellular sorting / Golgi / MDCK cells / Bartter syndrome / immunoprecipitation / エンドソーム / ライソゾーム / neuronal ceroid lipofuscinosis / ノックアウトマウス / トランスジェニックマウス / F1F0-ATPase / Iysosomal storage disease / クロライドチャネル / 水チャネル |
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| Research Abstract |
1) We generated transgenic mice expressing GFP under the control of CLC-KB gene promoter. It clearly determined the sites of intrarenal expression of CLC-KB.
2) We generated CLC-3 KO mice, and found that CLC-3 is functioning in intracellular acidic organelles, and that it is involved in protein-degradation pathways.
3) We successfully isolated fish CLC-K channel. This provided us information on the ancient role of CLC-K channels.
4) We determined the molecular pathogenesis of Bartter's syndrome by barttin mutations in mammalian cells. In immunocytochemistry, CLC-K2 was retained in the Golgi in the absence of barttin expression, but delivered to the plasma membrane when barttin was present. Bartlin was co-precipitated with CLC-K2, suggesting a protein-protein interaction. Disease-causing mutant barttins, especially R8L, were retained intracellularly, but their binding ability to CLC-K2 was preserved. This led to a retention of CLC-K2 in intracellular organelles with barttin, and a loss of plasma membrane localization.
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Report
(3 results)
Research Products
(19 results)
