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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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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. |
format | Online Article Text |
id | pubmed-7041696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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