Abstract
Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are key actin regulators that localize at regions of dynamic actin remodeling, including cellular protrusions and cell-cell and cell-matrix junctions. Several studies have suggested that Ena/VASP proteins are involved in the formation and function of cellular junctions. Here, we establish the importance of Ena/VASP in endothelial junctions in vivo by analysis of Ena/VASP-deficient animals. In the absence of Ena/VASP, the vasculature exhibits patterning defects and lacks structural integrity, leading to edema, hemorrhaging, and late stage embryonic lethality. In endothelial cells, we find that Ena/VASP activity is required for normal F-actin content, actomyosin contractility, and proper response to shear stress. These findings demonstrate that Ena/VASP is critical for actin cytoskeleton remodeling events involved in the maintenance of functional endothelia.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / physiology
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Actomyosin / physiology
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Animals
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Aorta / cytology
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Aorta / embryology
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Blood Vessels / pathology
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Blood Vessels / ultrastructure
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Cell Adhesion Molecules / deficiency
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Cell Adhesion Molecules / physiology*
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Cells, Cultured
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Cytoskeleton / physiology
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Edema / genetics
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Edema / pathology
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Embryo, Mammalian
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Endothelial Cells / physiology*
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Endothelium, Vascular / cytology
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Female
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Heart / embryology
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Hemorrhage / genetics
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Hemorrhage / pathology
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Humans
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Immunohistochemistry
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Intercellular Junctions / metabolism
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Mice
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Mice, Knockout
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Microfilament Proteins / deficiency
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Microfilament Proteins / physiology*
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Phosphoproteins / deficiency
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Phosphoproteins / physiology*
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Pregnancy
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Umbilical Veins / cytology
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Umbilical Veins / embryology
Substances
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Actins
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Cell Adhesion Molecules
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Microfilament Proteins
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Phosphoproteins
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Platelet Endothelial Cell Adhesion Molecule-1
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vasodilator-stimulated phosphoprotein
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Actomyosin