Blood Vessel Tubulogenesis Requires Rasip1 Regulation of GTPase Signaling
Cardiovascular function depends on patent blood vessel formation by endothelial cells (ECs). However, the mechanisms underlying vascular “tubulogenesis” are only beginning to be unraveled. We show that endothelial tubulogenesis requires the Ras interacting protein 1, Rasip1, and its binding partner,...
Gespeichert in:
Veröffentlicht in: | Developmental cell 2011-04, Vol.20 (4), p.526-539 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Cardiovascular function depends on patent blood vessel formation by endothelial cells (ECs). However, the mechanisms underlying vascular “tubulogenesis” are only beginning to be unraveled. We show that endothelial tubulogenesis requires the Ras interacting protein 1, Rasip1, and its binding partner, the RhoGAP Arhgap29. Mice lacking Rasip1 fail to form patent lumens in all blood vessels, including the early endocardial tube. Rasipl null angioblasts fail to properly localize the polarity determinant Par3 and display defective cell polarity, resulting in mislocalized junctional complexes and loss of adhesion to extracellular matrix (ECM). Similarly, depletion of either Rasip1 or Arhgap29 in cultured ECs blocks in vitro lumen formation, fundamentally alters the cytoskeleton, and reduces integrin-dependent adhesion to ECM. These defects result from increased RhoA/ROCK/myosin II activity and blockade of Cdc42 and Rac1 signaling. This study identifies Rasip1 as a unique, endothelial-specific regulator of Rho GTPase signaling, which is essential for blood vessel morphogenesis.
[Display omitted]
► Rasip1 is indispensible for mammalian blood vessel tubulogenesis ► Rasip1 associates with RhoGAP Arhgap29 and NMHCIIA in endothelial cells ► Rasip1 modulates Rho GTPase signaling by RhoA suppression and Cdc42/Rac1 activation ► Rasip1 is required for endothelial cell polarity and adhesion |
---|---|
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/j.devcel.2011.02.010 |