Cargando…

Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors

Actin polymerization is a universal mechanism to drive plasma membrane protrusion in motile cells. One apparent exception to this rule is continuing or even accelerated outgrowth of neuronal processes in the presence of actin polymerization inhibitors. This fact, together with the key role of microt...

Descripción completa

Detalles Bibliográficos
Autores principales: Chia, Jonathan X., Efimova, Nadia, Svitkina, Tatyana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170553/
https://www.ncbi.nlm.nih.gov/pubmed/27682586
http://dx.doi.org/10.1091/mbc.E16-04-0253
_version_ 1782483781770280960
author Chia, Jonathan X.
Efimova, Nadia
Svitkina, Tatyana M.
author_facet Chia, Jonathan X.
Efimova, Nadia
Svitkina, Tatyana M.
author_sort Chia, Jonathan X.
collection PubMed
description Actin polymerization is a universal mechanism to drive plasma membrane protrusion in motile cells. One apparent exception to this rule is continuing or even accelerated outgrowth of neuronal processes in the presence of actin polymerization inhibitors. This fact, together with the key role of microtubule dynamics in neurite outgrowth, led to the concept that microtubules directly drive plasma membrane protrusion either in the course of polymerization or by motor-driven sliding. The possibility that unextinguished actin polymerization drives neurite outgrowth in the presence of actin drugs was not explored. We show that cultured hippocampal neurons treated with cytochalasin D or latrunculin B contained dense accumulations of branched actin filaments at ∼50% of neurite tips at all tested drug concentrations (1–10 μM). Actin polymerization is required for neurite outgrowth because only low concentrations of either inhibitor increased the length and/or number of neurites, whereas high concentrations inhibited neurite outgrowth. Of importance, neurites undergoing active elongation invariably contained a bright F-actin patch at the tip, whereas actin-depleted neurites never elongated, even though they still contained dynamic microtubules. Stabilization of microtubules by Taxol treatment did not stop elongation of cytochalasin–treated neurites. We conclude that actin polymerization is indispensable for neurite elongation.
format Online
Article
Text
id pubmed-5170553
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-51705532017-01-30 Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors Chia, Jonathan X. Efimova, Nadia Svitkina, Tatyana M. Mol Biol Cell Articles Actin polymerization is a universal mechanism to drive plasma membrane protrusion in motile cells. One apparent exception to this rule is continuing or even accelerated outgrowth of neuronal processes in the presence of actin polymerization inhibitors. This fact, together with the key role of microtubule dynamics in neurite outgrowth, led to the concept that microtubules directly drive plasma membrane protrusion either in the course of polymerization or by motor-driven sliding. The possibility that unextinguished actin polymerization drives neurite outgrowth in the presence of actin drugs was not explored. We show that cultured hippocampal neurons treated with cytochalasin D or latrunculin B contained dense accumulations of branched actin filaments at ∼50% of neurite tips at all tested drug concentrations (1–10 μM). Actin polymerization is required for neurite outgrowth because only low concentrations of either inhibitor increased the length and/or number of neurites, whereas high concentrations inhibited neurite outgrowth. Of importance, neurites undergoing active elongation invariably contained a bright F-actin patch at the tip, whereas actin-depleted neurites never elongated, even though they still contained dynamic microtubules. Stabilization of microtubules by Taxol treatment did not stop elongation of cytochalasin–treated neurites. We conclude that actin polymerization is indispensable for neurite elongation. The American Society for Cell Biology 2016-11-15 /pmc/articles/PMC5170553/ /pubmed/27682586 http://dx.doi.org/10.1091/mbc.E16-04-0253 Text en © 2016 Chia et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Chia, Jonathan X.
Efimova, Nadia
Svitkina, Tatyana M.
Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title_full Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title_fullStr Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title_full_unstemmed Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title_short Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
title_sort neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170553/
https://www.ncbi.nlm.nih.gov/pubmed/27682586
http://dx.doi.org/10.1091/mbc.E16-04-0253
work_keys_str_mv AT chiajonathanx neuriteoutgrowthisdrivenbyactinpolymerizationeveninthepresenceofactinpolymerizationinhibitors
AT efimovanadia neuriteoutgrowthisdrivenbyactinpolymerizationeveninthepresenceofactinpolymerizationinhibitors
AT svitkinatatyanam neuriteoutgrowthisdrivenbyactinpolymerizationeveninthepresenceofactinpolymerizationinhibitors