Mechanosensing through focal adhesion‐anchored intermediate filaments

Gregor, Martin; Osmanagic‐Myers, Selma; Burgstaller, Gerald; Wolfram, Michael; Fischer, Ilse; Walko, Gernot; Resch, Guenter P.; Jörgl, Almut; Herrmann, Harald; Wiche, Gerhard

doi:10.1096/fj.13-231829

Cited by 147 publications

(187 citation statements)

References 65 publications

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“…Ligand-mediated transendocytosis of the receptor produce a strain on the receptor, a process that requires assembly of actin filaments at the membrane (42). Vimentin binds actin (64), while also regulating cytoskeletal tension (65) and actin filament contractility at the membrane (60). Hence, vimentin might link Jagged to the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Antfolk

Sjöqvist

Cheng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Notch signaling is a key regulator of angiogenesis, in which sprouting is regulated by an equilibrium between inhibitory Dll4-Notch signaling and promoting Jagged-Notch signaling. Whereas Fringe proteins modify Notch receptors and strengthen their activation by Dll4 ligands, other mechanisms balancing Jagged and Dll4 signaling are yet to be described. The intermediate filament protein vimentin, which has been previously shown to affect vascular integrity and regenerative signaling, is here shown to regulate ligand-specific Notch signaling. Vimentin interacts with Jagged, impedes basal recycling endocytosis of ligands, but is required for efficient receptor ligand transendocytosis and Notch activation upon receptor binding. Analyses of Notch signal activation by using chimeric ligands with swapped intracellular domains (ICDs), demonstrated that the Jagged ICD binds to vimentin and contributes to signaling strength. Vimentin also suppresses expression of Fringe proteins, whereas depletion of vimentin enhances Fringe levels to promote Dll4 signaling. In line with these data, the vasculature in vimentin knockout (VimKO) embryos and placental tissue is underdeveloped with reduced branching. Disrupted angiogenesis in aortic rings from VimKO mice and in endothelial 3D sprouting assays can be rescued by reactivating Notch signaling by recombinant Jagged ligands. Taken together, we reveal a function of vimentin and demonstrate that vimentin regulates Notch ligand signaling activities during angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Antfolk

Sjöqvist

Cheng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…However, this response appears to be specific to the cell type. In fibroblasts, plectin is necessary for localisation of vimentin intermediate filaments to focal adhesions at the cell periphery (Burgstaller et al, 2010;Spurny et al, 2008) and inhibits cell motility (Gregor et al, 2014). MCF-7 breast cancer cells similarly acquire a slower, less-protrusive phenotype in the absence of plectin (Boczonadi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes

Almeida

Walko

McMillan

et al. 2015

Journal of Cell Science

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The transmission of mechanical forces to the nucleus is important for intracellular positioning, mitosis and cell motility, yet the contribution of specific components of the cytoskeleton to nuclear mechanotransduction remains unclear. In this study, we examine how crosstalk between the cytolinker plectin and F-actin controls keratin network organisation and the 3D nuclear morphology of keratinocytes. Using micro-patterned surfaces to precisely manipulate cell shape, we find that cell adhesion and spreading regulate the size and shape of the nucleus. Disruption of the keratin cytoskeleton through loss of plectin facilitated greater nuclear deformation, which depended on actomyosin contractility. Nuclear morphology did not depend on direct linkage of the keratin cytoskeleton with the nuclear membrane, rather loss of plectin reduced keratin filament density around the nucleus. We further demonstrate that keratinocytes have abnormal nuclear morphologies in the epidermis of plectin-deficient, epidermolysis bullosa simplex patients. Taken together, our data demonstrate that plectin is an essential regulator of nuclear morphology in vitro and in vivo and protects the nucleus from mechanical deformation.

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“…Previous work demonstrated a role of plectins in coupling intermediate filaments to focal adhesions (Burgstaller et al, 2010;Gregor et al, 2014). However, contribution of plectins in functional interplay between myosin-II-containing stress fibers and intermediate filaments has not been reported.…”

Section: Effects Of Vimentin Depletion On Stress Fiber Organizationmentioning

confidence: 97%

Bidirectional Interplay between Vimentin Intermediate Filaments and Contractile Actin Stress Fibers

et al. 2015

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The actin cytoskeleton and cytoplasmic intermediate filaments contribute to cell migration and morphogenesis, but the interplay between these two central cytoskeletal elements has remained elusive. Here, we find that specific actin stress fiber structures, transverse arcs, interact with vimentin intermediate filaments and promote their retrograde flow. Consequently, myosin-II-containing arcs are important for perinuclear localization of the vimentin network in cells. The vimentin network reciprocally restricts retrograde movement of arcs and hence controls the width of flat lamellum at the leading edge of the cell. Depletion of plectin recapitulates the vimentin organization phenotype of arc-deficient cells without affecting the integrity of vimentin filaments or stress fibers, demonstrating that this cytoskeletal cross-linker is required for productive interactions between vimentin and arcs. Collectively, our results reveal that plectin-mediated interplay between contractile actomyosin arcs and vimentin intermediate filaments controls the localization and dynamics of these two cytoskeletal systems and is consequently important for cell morphogenesis.

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Mechanosensing through focal adhesion‐anchored intermediate filaments

Cited by 147 publications

References 65 publications

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes

Bidirectional Interplay between Vimentin Intermediate Filaments and Contractile Actin Stress Fibers

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