Transbilayer lipid asymmetry and cholestasis
| Project/Area Number |
26460065
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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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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Shin Hye-Won 京都大学, 薬学研究科, 准教授 (10345598)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 生体膜 / リン脂質 / 非対称性 / 細胞 / 胆汁酸 / P4-ATPase / PFIC / 胆汁うっ滞症 / 膜ダイナミクス / 胆汁うっ滞 |
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| Outline of Final Research Achievements |
Progressive familial intrahepatic cholestasis (PFIC) is a severe liver disease caused by impaired bile flow. PFIC type 1 (PFIC1) results from mutations in the ATP8B1 (flippase) protein. Although ATP8B1 has been hypothesized to mediate translocation of phosphatidylserine (PS) at the plasma membrane, it is unclear whether a defect in the phospholipid flippase activity of ATP8B1 is related to cholestasis. In this study, we found that ATP8B1 mediates the translocation of phosphatidylcholine (PC), but not PS, at the plasma membrane. The majority of missense mutations found in progressive familial intrahepatic cholestasis1 (PFIC1) patients reduced expression of ATP8B1 at the plasma membrane. Importantly, however, some missense mutants failed to translocate PC, although they were expressed normally at the plasma membrane. These findings implicate defects in the PC flippase activity of ATP8B1 in cholestasis and provide important insights into the pathophysiological mechanisms of PFIC1.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Class I Arfs (Arf1 and Arf3) and Arf6 are localized to the Flemming body and play important roles in cytokinesis.2016
Author(s)
Hanai, A., Ohgi, M., Yagi, C., Ueda, T., Shin, H.-W., and Nakayama, K.
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Journal Title
Journal of Biochemistry
Volume: 159
Issue: 2
Pages: 201-208
DOI
Related Report
Peer Reviewed
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[Journal Article] COPI-mediated retrieval of SCAP is critical for regulating lipogenesis under basal and sterol-deficient conditions.2015
Author(s)
Takashima, K., Saitoh, A., Funabashi, T., Hirose, S., Yagi, C., Nozaki, S., Sato, R., Shin, H.-W., and Nakayama, K.
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Journal Title
Journal of Cell Science
Volume: 128
Pages: 2805-2815
DOI
Related Report
Peer Reviewed
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[Journal Article] Phospholipid flippase ATP10A translocates phosphatidylcholine and is involved in plasma membrane dynamics.2015
Author(s)
Naito, T., Takatsu, H., Miyano, R., Takada, N., Nakayama, K., and Shin, H.-W.
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Journal Title
Journal of Biological Chemistry
Volume: 290
Issue: 24
Pages: 15004-15017
DOI
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Phospholipid Flippase Activities and Substrate Specificities of Human Type IV P-type ATPases Localized to the Plasma Membrane2014
Author(s)
Takatsu, H., Tanaka, G., Segawa, K., Suzuki, J., Nagata, S., Nakayama, K. and Shin, H.W.
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Journal Title
J. Biol. Chem
Volume: 289
Issue: 48
Pages: 33543-33556
DOI
NAID
Related Report
Peer Reviewed / Open Access
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