Regulation of retrograde transport mediated by LRRK1-Dynein complex
| Project/Area Number |
15H04697
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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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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | LRRK1 / EGFR / CLIP170 / Rab7 / 細胞内トラフィック / Dynein / オートファゴソーム / エンドソーム |
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| Outline of Final Research Achievements |
From this study, we revealed that (1) LRRK1 functions to initiate the transport of EGFR-containing endosom along microtubules through the phosphorylation of a microtubule plus end-binding factor CLIP-170 and the promotion of its binding to p150Glued. Furthermore, we revealed that (2) LRRK1 phosphorylates Ser-72 located in the SwitchII region of Rab7 and selectively promotes the binding between Rab7 and RILP. In addition, we revealed that (3) LRRK1 was activated in the M-phase centrosome and phosphorylates the centrosome component CDK5RAP2. This functions in the regulation of spindle orientation by promoting g-tubulin-dependent microtubule nucleation.
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| Academic Significance and Societal Importance of the Research Achievements |
ある種の癌細胞では、EGFRシグナルが過剰になっている。我々はLRRK1が、EGFRの細胞内トラフィックを制御することで、EGFRシグナルを負に制御することを明らかにした。このことは、過剰なEGFRシグナルが引き起こす細胞癌化に対し、それを防ぐ手立てを開発するのに役立つ可能性がある。さらにLRRK1のファミリー分子LRRK2は、家族性パーキンソン病原因遺伝子（Park8）であるが、その作用機序や生理的役割・パーキンソン病発症機構は依然として不明なままである。LRRK1とLRRK2は一部共通の機構で機能しており、LRRK1の機能解析はLRRK2の作用機構解明に繋がる可能性がある。
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Report
(4 results)
Research Products
(7 results)
