| Project/Area Number |
18K06865
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Yokohama College of Pharmacy (2020)
University of Occupational and Environmental Health, Japan (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | TASKチャネル / TASK1チャネル / p11タンパク質 / PC12細胞 / TASK1 channel / endocytosis / PC12 cell / p11 / TASK channel |
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| Outline of Final Research Achievements |
I investigated the function and physiological role of TASK1 channels in endocrine cells. Pharmacological and molecular biological analyses showed that TASK1 channels are regulated by the clathrin-dependent endocytosis in NGF- and muscarine-stimulated adrenal medullary and PC12 cells. Furthermore, it showed that muscarine-induced endocytosis of TASK1 channels is regulated through PKC-Pyk2-Src pathway in PC12 cells. Additionally, TASK1 channels were localized at plasma membrane in PC12 cells is due to a lack of p11 protein. On the other hand, the treatment with NGF of PC12 cells was induced the expression of p11 proteins and resulted in a change in membrane localization of TASK1 channels. These results indicate that TASK1 channels were translocated and localized to plasma membrane by dissociating from p11 proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、TASK1チャネルの機能調節機構を明らかにした。ムスカリン受容体によるKチャネルの抑制は、多くのチャネルが、gatingの変化によって制御されていることが知られている。今回申請者は、Kチャネルの1つであるTASK1チャネルの抑制には、gatingの変化だけでなくエンドサイトーシスが関与することを世界で初めて明らかにした。本研究成果は、TASKチャネルファミリーの機能制御機構を明らかにするとともに、未解明の多くのKチャネルの機能制御機構の解明を推進するものと期待され、学術的意義は高い。
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