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

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Jiu , Y , Peränen , J , Schaible , N , Cheng , F , Eriksson , J E , Krishnan , R & Lappalainen , P 2017 , ' Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA ' , Journal of Cell Science , vol. 130 , no. 5 , pp. 892-902 . https://doi.org/10.1242/jcs.196881

Title: Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
Author: Jiu, Yaming; Peränen, Johan; Schaible, Niccole; Cheng, Fang; Eriksson, John E.; Krishnan, Ramaswamy; Lappalainen, Pekka
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
University of Helsinki, Univ Turku, Turku Ctr Biotechnol
University of Helsinki, Institute of Biotechnology
Date: 2017-03-01
Language: eng
Number of pages: 11
Belongs to series: Journal of Cell Science
ISSN: 0021-9533
URI: http://hdl.handle.net/10138/183465
Abstract: 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.
Subject: Vimentin
Intermediate filament
Actin
Stress fiber
RhoA
GEF-H1
NUCLEOTIDE EXCHANGE FACTOR
IN-VIVO
MECHANICAL FORCE
PROSTATE-CANCER
RHOGEF GEF-H1
CELLS
ADHESION
KINASE
CYTOSKELETON
ACTIVATION
1182 Biochemistry, cell and molecular biology
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