Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation
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Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation. / Lund, Natalie; Henrion, Daniel; Tiede, Petra; Ziche, Marina; Schunkert, Heribert; Ito, Wulf D.
in: BIOCHEM BIOPH RES CO, Jahrgang 395, Nr. 3, 07.05.2010, S. 401-406.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation
AU - Lund, Natalie
AU - Henrion, Daniel
AU - Tiede, Petra
AU - Ziche, Marina
AU - Schunkert, Heribert
AU - Ito, Wulf D
N1 - Copyright (c) 2010 Elsevier Inc. All rights reserved.
PY - 2010/5/7
Y1 - 2010/5/7
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Adhesion Molecules/metabolism
KW - Cell Movement
KW - Cell Proliferation
KW - Cyclic GMP-Dependent Protein Kinases/metabolism
KW - Endothelial Cells/cytology
KW - Mice
KW - Mice, Knockout
KW - Microfilament Proteins/metabolism
KW - Phosphoproteins/metabolism
KW - Phosphorylation
KW - Rats
KW - Serine/metabolism
KW - Vimentin/biosynthesis
U2 - 10.1016/j.bbrc.2010.04.033
DO - 10.1016/j.bbrc.2010.04.033
M3 - SCORING: Journal article
C2 - 20382123
VL - 395
SP - 401
EP - 406
JO - BIOCHEM BIOPH RES CO
JF - BIOCHEM BIOPH RES CO
SN - 0006-291X
IS - 3
ER -