NuMA1 promotes axon initial segment assembly through inhibition of endocytosis

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. Rasband

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageBritish English
JournalJournal of Cell Biology
Volume219
Issue number2
DOIs
StatePublished - 3 Feb 2020

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