Intracellular logistics of LIS1-cytoplasmic dynein in lissencephaly.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293066
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: University of Fukui (2016-2017); Osaka City University (2014-2015)
• Principal Investigator: Yamada Masami 福井大学, 学術研究院医学系部門, 教授 (10322851)
• Project Period (FY): 2014-04-01 – 2018-03-31
• 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

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.

Free Research Field

細胞生物学、生化学、神経科学