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FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption
Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs disp...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275378/ https://www.ncbi.nlm.nih.gov/pubmed/22312004 http://dx.doi.org/10.1083/jcb.201105154 |
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author | Nechipurenko, Inna V. Broihier, Heather T. |
author_facet | Nechipurenko, Inna V. Broihier, Heather T. |
author_sort | Nechipurenko, Inna V. |
collection | PubMed |
description | Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs displayed augmented MT stability. In contrast, motor neuronal overexpression of wild-type FoxO moderately destabilized MTs, whereas overexpression of constitutively nuclear FoxO severely destabilized MTs. Thus, FoxO negatively regulates synaptic MT stability. FoxO family members are well-established components of stress-activated feedback loops. We hypothesized that FoxO might also be regulated by cytoskeletal stress because it was well situated to shape neuronal MT organization after cytoskeletal damage. Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton. This decrease was independent of the dual leucine zipper kinase–Wallenda pathway and required function of Akt kinase. We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult. |
format | Online Article Text |
id | pubmed-3275378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32753782012-08-06 FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption Nechipurenko, Inna V. Broihier, Heather T. J Cell Biol Research Articles Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs displayed augmented MT stability. In contrast, motor neuronal overexpression of wild-type FoxO moderately destabilized MTs, whereas overexpression of constitutively nuclear FoxO severely destabilized MTs. Thus, FoxO negatively regulates synaptic MT stability. FoxO family members are well-established components of stress-activated feedback loops. We hypothesized that FoxO might also be regulated by cytoskeletal stress because it was well situated to shape neuronal MT organization after cytoskeletal damage. Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton. This decrease was independent of the dual leucine zipper kinase–Wallenda pathway and required function of Akt kinase. We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult. The Rockefeller University Press 2012-02-06 /pmc/articles/PMC3275378/ /pubmed/22312004 http://dx.doi.org/10.1083/jcb.201105154 Text en © 2012 Nechipurenko and Broihier 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Nechipurenko, Inna V. Broihier, Heather T. FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title | FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title_full | FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title_fullStr | FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title_full_unstemmed | FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title_short | FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption |
title_sort | foxo limits microtubule stability and is itself negatively regulated by microtubule disruption |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275378/ https://www.ncbi.nlm.nih.gov/pubmed/22312004 http://dx.doi.org/10.1083/jcb.201105154 |
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