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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Jiu Y, Peranen J, Schaible N, Cheng F, Eriksson JE, Krishnan R, Lappalainen P
Publisher: COMPANY OF BIOLOGISTS LTD
Publication year: 2017
Journal: Journal of Cell Science
Journal acronym: J CELL SCI
Volume number: 130
Start page: 892
End page: 902
Number of pages: 11
ISSN: 0021-9533


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.


Keywords

GEF-H1, Intermediate filament, RhoA, Stress fiber, Vimentin

Last updated on 2019-21-11 at 04:53