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タイトル: | Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics |
著者: | Jin, Mingyue Pomp, Oz Shinoda, Tomoyasu Toba, Shiori Torisawa, Takayuki Furuta, Ken’ya Oiwa, Kazuhiro Yasunaga, Takuo Kitagawa, Daiju Matsumura, Shigeru Miyata, Takaki Tan, Thong Teck Reversade, Bruno Hirotsune, Shinji |
著者名の別形: | 松村, 繁 |
発行日: | 12-Jan-2017 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 7 |
論文番号: | 39902 |
抄録: | Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 is essential for aster formation and maintenance in vitro. siRNA-mediated depletion of p80 and/or NuMA induced abnormal mitotic phenotypes in cultured mouse embryonic fibroblasts and aberrant neurogenesis and neuronal migration in the mouse embryonic brain. Importantly, these results were confirmed in p80-mutant harboring patient-derived induced pluripotent stem cells and brain organoids. Taken together, our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via MT organization at the centrosome/spindle pole. |
著作権等: | © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/218746 |
DOI(出版社版): | 10.1038/srep39902 |
PubMed ID: | 28079116 |
出現コレクション: | 学術雑誌掲載論文等 |
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