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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...

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Detalles Bibliográficos
Autores principales: Nechipurenko, Inna V., Broihier, Heather T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
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.
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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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