Understanding of mechanism underlying intracellular sorting of hepatocanalicular transporters
| Project/Area Number |
23790175
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | トランスポーター / 肝内胆汁うっ滞 / 細胞内ソーティング / 胆汁酸 / フェニルブ チレート / コレステロール / ABCトランスポーター / 肝細胞 / ユビキチン |
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| Research Abstract |
Bile salt export pump (BSEP) localizes on canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. BSEP dysfunction attributed to its internalization from hepatocanalicular membrane and subsequent degradation causes intrahepatic cholestasis. At present, no medical therapy for this disease state has been established, because the regulatory mechanism of cell surface expression of BSEP remains to be elucidated. In this study, we explored it focusing on posttranslational machinery and demonstrated that ubiquitination, a posttranslational modification, of BSEP plays a role in its internalization via clathrin-mediated endocytosis involving the AP2 adaptor complex,an adaptor protein required for cargo selection in clathrin-mediated endocytosis.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function.2012
Author(s)
Hayashi H, Inamura K, Aida K, Naoi S, Horikawa R, Nagasaka H, Takatani T, Fukushima T, Hattori A, Yabuki T, Horii I, Sugiyama Y.
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Journal Title
Hepatology.
Volume: 55(6)
Pages: 1889-900
Related Report
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[Journal Article] Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4) and mediates the internalization of MRP4.2012
Author(s)
Hayashi H, Naoi S, Nakagawa T, Nishikawa T, Fukuda H, Imajoh-OhmiS, Kondo A, Kubo K, Yabuki T, HattoriA, Hirouchi M, Sugiyama Y
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Journal Title
J Biol Chem.
Volume: 287
Pages: 15054-15065
DOI
Related Report
Peer Reviewed
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