Regulation of membrane traffic by ROCO family kinase LRRK1/2
| Project/Area Number |
18H02612
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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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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Nagoya University |
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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 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | LRRK1 / EGFR / Mitophagy / Rab7 / membrane traffic / Rab / endosome / LRRK2 |
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| Outline of Final Research Achievements |
In this study, we focused on the function of LRRK1 in (1) EGFR intracellular trafficking and (2) mitophagy, a selective autophagy to remove damaged mitochondria. Regarding (1), we found that LRRK1 and the phosphatase PTEN regulate EGFR intracellular trafficking by phosphorylating and dephosphorylating small G protein Rab7, respectively. Regarding (2), LRRK1 is phosphorylated and activated by ULK1, which phosphorylates Rab7 on damaged mitochondria and recruits ATG9, an important factor for the formation of isolation membrane. We also found that LRRK1 may competitively regulate mitophagy with LRRK2.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞の癌化メカニズムの解明や、パーキンソン病など脳変性疾患の発症メカニズムの解明は、高齢化社会にある日本において喫緊の課題である。本研究からLRRK1-Rab7経路によるEGFRリソソーム分解機構の一端が明らかとなり、細胞癌化の理解に貢献できた。またパーキンソン病発症に重要と考えられているマイトファジーに関し、LRRK1がParkin依存的な損傷ミトコンドリア除去に必須であることを明らかにした。本研究成果は、マイトファジーの新たな一面を明らかにしただけでなく、LRRK2によるマイトファジー制御にも新たな視点を与えるものである。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration.2018
Author(s)
Hisamoto, N., Tsuge, A., Pastuhov, S., Shimizu, T., Hanafusa, H., Matsumoto, K.
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Journal Title
Nature Commun.
Volume: 9
Issue: 1
Pages: 3099-3099
DOI
Related Report
Peer Reviewed / Open Access
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