Ena/VASP is required for endothelial barrier function in vivo.
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.
Furman
Craig
C
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sieminski
Alisha L
AL
Kwiatkowski
Adam V
AV
Rubinson
Douglas A
DA
Vasile
Eliza
E
Bronson
Roderick T
RT
Fässler
Reinhard
R
Gertler
Frank B
FB
D000199:Actins / Q000502:physiology; D000205:Actomyosin / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D004487:Edema / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006321:Heart / Q000196:embryology; D006470:Hemorrhage / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000502:physiology*; D010750:Phosphoproteins / Q000172:deficiency / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D014471:Umbilical Veins / Q000166:cytology / Q000196:embryology; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000098662:Vasodilator-Stimulated Phosphoprotein; D000205:Actomyosin