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Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation

Abstract :

The cytoskeleton plays a central role for the integration of biochemical and biomechanical signals across the cell required for complex cellular functions. Recent studies indicate that the intermediate filament vimentin is necessary for endothelial cell morphogenesis e.g. in the context of leukocyte transmigration. Here, we present evidence, that the scaffold provided by vimentin is essential for VASP localization and PKG mediated VASP phosphorylation and thus controls endothelial cell migration and proliferation. Vimentin suppression using siRNA technique significantly decreased migration velocity by 50% (videomicroscopy), diminished transmigration activity by 42.5% (Boyden chamber) and reduced proliferation by 43% (BrdU-incorporation). In confocal microscopy Vimentin colocalized with VASP and PKG in endothelial cells. Vimentin suppression was accompanied with a translocation of VASP from focal contacts to the perinuclear region. VASP/Vimentin and PKG/Vimentin colocalization appeared to be essential for proper PKG mediated VASP phosphorylation because we detected a diminished expression of PKG and p(Ser239)-VASP in vimentin-suppressed cells, Furthermore, the induction of VASP phosphorylation in perfused arteries was markedly decreased in vimentin knockout mice compared to wildtypes. A link is proposed between vimentin, VASP phosphorylation and actin dynamics that delivers an explanation for the important role of vimentin in controlling endothelial cell morphogenesis.

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https://hal.univ-angers.fr/hal-03408517
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Soumis le : vendredi 29 octobre 2021 - 10:51:40
Dernière modification le : samedi 30 octobre 2021 - 03:58:02

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N. Lund, Daniel Henrion, P. Tiede, M. Ziche, H. Schunkert, et al.. Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation. Biochemical and biophysical research communications, 2010, 395 (3), pp.401 - 406. ⟨10.1016/j.bbrc.2010.04.033⟩. ⟨hal-03408517⟩

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