論文

2019年11月14日

NuMA1 promotes axon initial segment assembly through inhibition of endocytosis

The Journal of Cell Biology
  • Tomohiro Torii
  • ,
  • Yuki Ogawa
  • ,
  • Cheng-Hsin Liu
  • ,
  • Tammy Szu-Yu Ho
  • ,
  • Hamdan Hamdan
  • ,
  • Chih-chuan Wang
  • ,
  • Juan A. Oses-Prieto
  • ,
  • Alma L. Burlingame
  • ,
  • Matthew N. Rasb

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1083/jcb.201907048
出版者・発行元
Rockefeller University Press

<jats:p>Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. However, the mechanisms controlling AIS assembly remain poorly defined. We performed differential proteomics and found nuclear mitotic apparatus protein 1 (NuMA1) is downregulated in AIS-deficient neonatal mouse brains and neurons. NuMA1 is transiently located at the AIS during development where it interacts with the scaffolding protein 4.1B and the dynein regulator lissencephaly 1 (Lis1). Silencing NuMA1 or protein 4.1B by shRNA disrupts AIS assembly, but not maintenance. Silencing Lis1 or overexpressing NuMA1 during AIS assembly increased the density of AIS proteins, including ankyrinG and neurofascin-186 (NF186). NuMA1 inhibits the endocytosis of AIS NF186 by impeding Lis1’s interaction with doublecortin, a potent facilitator of NF186 endocytosis. Our results indicate the transient expression and AIS localization of NuMA1 stabilizes the developing AIS by inhibiting endocytosis and removal of AIS proteins.</jats:p>

リンク情報
DOI
https://doi.org/10.1083/jcb.201907048
ID情報
  • DOI : 10.1083/jcb.201907048
  • ISSN : 0021-9525
  • ISSN : 1540-8140
  • ORCIDのPut Code : 107660027

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