Elucidation of molecular mechanism of proteinuria mediated by Cubilin
| Project/Area Number |
18K07872
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Harita Yutaka 東京大学, 医学部附属病院, 准教授 (10451866)
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| Co-Investigator(Kenkyū-buntansha) |
神田 祥一郎 東京大学, 医学部附属病院, 講師 (60632651)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 蛋白尿 / 尿細管 / Cubilin / Amnionless / アルブミン / NVL / 再吸収 / エンドサイトーシス / 近位尿細管 / 低分子蛋白尿 |
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| Outline of Final Research Achievements |
Cubilin (CUBN) and amnionless (AMN), expressed in kidney and intestine, form a multiligand receptor complex called CUBAM that plays a crucial role in albumin absorption. Here, we describe a quantitative assay to evaluate albumin uptake by CUBAM using cells expressing full-length CUBN and elucidate the crucial roles of the C-terminal part of CUBN and the endocytosis signal motifs of AMN in albumin endocytosis. We also demonstrate that nuclear valosin-containing protein-like 2 (NVL2), an interacting protein of AMN, is involved in this process. Although NVL2 was mainly localized in the nucleolus in cells without AMN expression, it was translocated to the extranuclear compartment when coexpressed with AMN. NVL2 knockdown significantly impaired internalization of the CUBN-albumin complex in cultured cells, demonstrating an involvement of NVL2 in endocytic regulation. These findings uncover a link between membrane and nucleolar proteins that is involved in endocytic processes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、尿細管における蛋白質の再吸収の新たな分子機序が明らかになった。蛋白尿は多くの腎疾患の発症進展において重要な役割を果たしており、そのメカニズムや治療標的を検討する上で重要な知見が得られた。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Deletion in the cobalamin synthetase W domain-containing protein 1 gene is associated with congenital anomalies of the kidney and urinary tract.2020
Author(s)
Kanda S, Ohmuraya M, Akagawa H, Horita S, Yoshida Y, Kaneko N, Sugawara N, Ishizuka K, Miura K, Harita Y, Yamamoto T, Oka A, Araki K, Furukawa T, Hattori M.
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Journal Title
J Am Soc Nephrol
Volume: 31
Issue: 1
Pages: 139-147
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis.2019
Author(s)
Hashimoto T, Harita Y, Takizawa K, Urae S, Ishizuka K, Miura K, Horita S, Ogino D, Tamiya G, Ishida H, Mitsui T, Hayasaka K, Hattori M.
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Journal Title
Kidney Int Rep
Volume: 4(9)
Issue: 9
Pages: 1312-1322
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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