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Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA

The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that...

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Autores principales: Jiu, Yaming, Peränen, Johan, Schaible, Niccole, Cheng, Fang, Eriksson, John E., Krishnan, Ramaswamy, Lappalainen, Pekka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358333/
https://www.ncbi.nlm.nih.gov/pubmed/28096473
http://dx.doi.org/10.1242/jcs.196881
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author Jiu, Yaming
Peränen, Johan
Schaible, Niccole
Cheng, Fang
Eriksson, John E.
Krishnan, Ramaswamy
Lappalainen, Pekka
author_facet Jiu, Yaming
Peränen, Johan
Schaible, Niccole
Cheng, Fang
Eriksson, John E.
Krishnan, Ramaswamy
Lappalainen, Pekka
author_sort Jiu, Yaming
collection PubMed
description The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2 (see Geeves et al., 2015). The vimentin-knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous ‘unit length form’ vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton. Finally, we provide evidence that the effects of vimentin on stress fibers are mediated by activation of RhoA through its guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2). Vimentin depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. Taken together, these data reveal a new mechanism by which intermediate filaments regulate contractile actomyosin bundles, and may explain why elevated vimentin expression levels correlate with increased migration and invasion of cancer cells.
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spelling pubmed-53583332017-04-10 Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA Jiu, Yaming Peränen, Johan Schaible, Niccole Cheng, Fang Eriksson, John E. Krishnan, Ramaswamy Lappalainen, Pekka J Cell Sci Research Article The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2 (see Geeves et al., 2015). The vimentin-knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous ‘unit length form’ vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton. Finally, we provide evidence that the effects of vimentin on stress fibers are mediated by activation of RhoA through its guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2). Vimentin depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. Taken together, these data reveal a new mechanism by which intermediate filaments regulate contractile actomyosin bundles, and may explain why elevated vimentin expression levels correlate with increased migration and invasion of cancer cells. The Company of Biologists Ltd 2017-03-01 /pmc/articles/PMC5358333/ /pubmed/28096473 http://dx.doi.org/10.1242/jcs.196881 Text en © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Jiu, Yaming
Peränen, Johan
Schaible, Niccole
Cheng, Fang
Eriksson, John E.
Krishnan, Ramaswamy
Lappalainen, Pekka
Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title_full Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title_fullStr Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title_full_unstemmed Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title_short Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
title_sort vimentin intermediate filaments control actin stress fiber assembly through gef-h1 and rhoa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358333/
https://www.ncbi.nlm.nih.gov/pubmed/28096473
http://dx.doi.org/10.1242/jcs.196881
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