Intracellular logistics of LIS1-cytoplasmic dynein in lissencephaly.
| Project/Area Number |
26293066
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | University of Fukui (2016-2017)
Osaka City University (2014-2015) |
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Principal Investigator |
Yamada Masami 福井大学, 学術研究院医学系部門, 教授 (10322851)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 滑脳症 / 神経変性疾患 / 細胞内物質輸送 / 微小管モーター / 微小管 / LIS1 / 細胞質ダイニン / シヌクレイン / 神経細胞遊走障害 / 蛍光分子イメージング / クラスIIIβ-チューブリン / α-シヌクレイン / 細胞内ロジスティクス / 微小管モータータンパク質 / カルパイン阻害薬 / 神経細胞移動障害 / mNUDC / クラスIIIベータ－チューブリン |
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| Outline of Final Research Achievements |
LIS1 was identified as the gene mutated in individuals with lissencephaly, which is a devastating neurological disorder caused by defective neuronal migration. We previously proposed a model for a mobile tubulin fragments (tMT), in which cytoplasmic dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport. However, the mechanisms that produce tMTs have not been determined.
Here, we identified α-synuclein by immunoprecipitation method with anti-β III-tubulin antibody, which has been linked to Parkinson’s disease and dementia. Live-cell imaging showed that α-synuclein co-transported with LIS1, dynein and tMT in the anterograde transport. Our in vitro investigations of microtubule dynamics revealed that α-synuclein regulated the polymerization/depolymerization of short microtubule fragment. Our findings indicate that α-synuclein facilitates to form short, mobile tMTs that play an important role in the axonal transport.
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] Alpha-synuclein binds unconventional microtubules that have a unique function.2017
Author(s)
Shiori Toba, Mingyue Jin, Masami Yamada, Kanako Kumamoto, Sakiko Matsumoto, Takuo Yasunaga, Yuko Fukunaga, Atsuo Miyazawa, Sakiko Fujita, Kyoko Itoh, Shinji Fushiki, Kojima Hiroaki, Hideki Wanibuchi, Yoshiyuki Arai, Takeharu Nagai, Shinji Hirotsune
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Journal Title
Scientific Reports
Volume: 7
Pages: 1-19
Related Report
Peer Reviewed / Open Access
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