Shroom2 regulates contractility to control endothelial morphogenesis.
The intrinsic contractile, migratory, and adhesive properties of endothelial cells are central determinants in the formation of vascular networks seen in vertebrate organisms. Because Shroom2 (Shrm2) is expressed within the endothelium, is localized to cortical actin and cell-cell adhesions, and contains a conserved Rho kinase (Rock) binding domain, we hypothesized that Shrm2 may participate in the regulation of endothelial cell behavior during vascular morphogenesis. Consistent with this hypothesis, depletion of Shrm2 results in elevated branching and sprouting angiogenic behavior of endothelial cells. This is recapitulated in human umbilical vein endothelial cells and in a vasculogenesis assay in which differentiated embryonic stem cells depleted for Shrm2 form a more highly branched endothelial network. Further analyses indicate that the altered behavior observed following Shrm2 depletion is due to aberrant cell contractility, as evidenced by decreased stress fiber organization and collagen contraction with an increase in cellular migration. Because Shrm2 directly interacts with Rock, and Shrm2 knockdown results in the loss of Rock and activated myosin II from sites of cell-cell adhesion, we conclude that Shrm2 facilitates the formation of a contractile network within endothelial cells, the loss of which leads to an increase in endothelial sprouting, migration, and angiogenesis.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Matthew J
MJ
Farber
Ryan
R
Rizaldy
Jeffrey D
JD
Hildebrand
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins; D009024:Morphogenesis / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D018919:Neovascularization, Physiologic; D034622:RNA Interference
D008565:Membrane Proteins; D008840:Microfilament Proteins; C101060:SHROOM2 protein, human; C484418:Shroom2 protein, mouse
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