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Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling
Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871425/ https://www.ncbi.nlm.nih.gov/pubmed/24344184 http://dx.doi.org/10.1083/jcb.201306032 |
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author | Wu, Congying Haynes, Elizabeth M. Asokan, Sreeja B. Simon, Jeremy M. Sharpless, Norman E. Baldwin, Albert S. Davis, Ian J. Johnson, Gary L. Bear, James E. |
author_facet | Wu, Congying Haynes, Elizabeth M. Asokan, Sreeja B. Simon, Jeremy M. Sharpless, Norman E. Baldwin, Albert S. Davis, Ian J. Johnson, Gary L. Bear, James E. |
author_sort | Wu, Congying |
collection | PubMed |
description | Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon Arp2/3 depletion, the expression of numerous genes encoding secreted factors, including chemokines, growth factors, and matrix metalloproteases, was increased, a signature resembling the senescence-associated secretory phenotype. These factors affected epidermal growth factor chemotaxis in a nonautonomous way, resolving the recent contradictions about the role of Arp2/3 in chemotaxis. We demonstrate that these genes were activated by nuclear factor κB via a CCM2–MEKK3 pathway that has been implicated in hyperosmotic stress signaling. Consistent with this, Arp2/3-depleted cells showed misregulation of volume control and reduced actin in the submembranous cortex. The defects in osmotic signaling in the Arp2/3-depleted cells can be rescued by hypoosmotic treatment. Thus, perturbations of Arp2/3 have nonautonomous effects that should be considered when evaluating experimental manipulations and diseases affecting the Arp2/3-actin cytoskeleton. |
format | Online Article Text |
id | pubmed-3871425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38714252014-06-23 Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling Wu, Congying Haynes, Elizabeth M. Asokan, Sreeja B. Simon, Jeremy M. Sharpless, Norman E. Baldwin, Albert S. Davis, Ian J. Johnson, Gary L. Bear, James E. J Cell Biol Research Articles Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon Arp2/3 depletion, the expression of numerous genes encoding secreted factors, including chemokines, growth factors, and matrix metalloproteases, was increased, a signature resembling the senescence-associated secretory phenotype. These factors affected epidermal growth factor chemotaxis in a nonautonomous way, resolving the recent contradictions about the role of Arp2/3 in chemotaxis. We demonstrate that these genes were activated by nuclear factor κB via a CCM2–MEKK3 pathway that has been implicated in hyperosmotic stress signaling. Consistent with this, Arp2/3-depleted cells showed misregulation of volume control and reduced actin in the submembranous cortex. The defects in osmotic signaling in the Arp2/3-depleted cells can be rescued by hypoosmotic treatment. Thus, perturbations of Arp2/3 have nonautonomous effects that should be considered when evaluating experimental manipulations and diseases affecting the Arp2/3-actin cytoskeleton. The Rockefeller University Press 2013-12-23 /pmc/articles/PMC3871425/ /pubmed/24344184 http://dx.doi.org/10.1083/jcb.201306032 Text en © 2013 Wu et al. 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 Wu, Congying Haynes, Elizabeth M. Asokan, Sreeja B. Simon, Jeremy M. Sharpless, Norman E. Baldwin, Albert S. Davis, Ian J. Johnson, Gary L. Bear, James E. Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title | Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title_full | Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title_fullStr | Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title_full_unstemmed | Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title_short | Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling |
title_sort | loss of arp2/3 induces an nf-κb–dependent, nonautonomous effect on chemotactic signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871425/ https://www.ncbi.nlm.nih.gov/pubmed/24344184 http://dx.doi.org/10.1083/jcb.201306032 |
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