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...
Autores principales: | , , |
---|---|
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 |