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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Jiu Y, Peranen J, Schaible N, Cheng F, Eriksson JE, Krishnan R, Lappalainen P
Förläggare: COMPANY OF BIOLOGISTS LTD
Publiceringsår: 2017
Tidskrift: Journal of Cell Science
Tidskriftsakronym: J CELL SCI
Volym: 130
Artikelns första sida, sidnummer: 892
Artikelns sista sida, sidnummer: 902
Antal sidor: 11
ISSN: 0021-9533


Abstrakt

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.


Nyckelord

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

Senast uppdaterad 2020-04-04 vid 04:24