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NuMA1 promotes axon initial segment assembly through inhibition of endocytosis

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...

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Autores principales: Torii, Tomohiro, Ogawa, Yuki, Liu, Cheng-Hsin, Ho, Tammy Szu-Yu, Hamdan, Hamdan, Wang, Chih-chuan, Oses-Prieto, Juan A., Burlingame, Alma L., Rasband, Matthew N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041696/
https://www.ncbi.nlm.nih.gov/pubmed/31727776
http://dx.doi.org/10.1083/jcb.201907048
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author Torii, Tomohiro
Ogawa, Yuki
Liu, Cheng-Hsin
Ho, Tammy Szu-Yu
Hamdan, Hamdan
Wang, Chih-chuan
Oses-Prieto, Juan A.
Burlingame, Alma L.
Rasband, Matthew N.
author_facet Torii, Tomohiro
Ogawa, Yuki
Liu, Cheng-Hsin
Ho, Tammy Szu-Yu
Hamdan, Hamdan
Wang, Chih-chuan
Oses-Prieto, Juan A.
Burlingame, Alma L.
Rasband, Matthew N.
author_sort Torii, Tomohiro
collection PubMed
description 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.
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spelling pubmed-70416962020-08-03 NuMA1 promotes axon initial segment assembly through inhibition of endocytosis Torii, Tomohiro Ogawa, Yuki Liu, Cheng-Hsin Ho, Tammy Szu-Yu Hamdan, Hamdan Wang, Chih-chuan Oses-Prieto, Juan A. Burlingame, Alma L. Rasband, Matthew N. J Cell Biol Research Articles 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. Rockefeller University Press 2019-11-14 /pmc/articles/PMC7041696/ /pubmed/31727776 http://dx.doi.org/10.1083/jcb.201907048 Text en © 2019 Torii et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Torii, Tomohiro
Ogawa, Yuki
Liu, Cheng-Hsin
Ho, Tammy Szu-Yu
Hamdan, Hamdan
Wang, Chih-chuan
Oses-Prieto, Juan A.
Burlingame, Alma L.
Rasband, Matthew N.
NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title_full NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title_fullStr NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title_full_unstemmed NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title_short NuMA1 promotes axon initial segment assembly through inhibition of endocytosis
title_sort numa1 promotes axon initial segment assembly through inhibition of endocytosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041696/
https://www.ncbi.nlm.nih.gov/pubmed/31727776
http://dx.doi.org/10.1083/jcb.201907048
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