Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782516216168972288 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5358333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT jiuyaming vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT peranenjohan vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT schaibleniccole vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT chengfang vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT erikssonjohne vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT krishnanramaswamy vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa AT lappalainenpekka vimentinintermediatefilamentscontrolactinstressfiberassemblythroughgefh1andrhoa |