Blood Vessel Tubulogenesis Requires Rasip1 Regulation of GTPase Signaling

Ke Xu, Anastasia Sacharidou, Stephen Fu, Diana C. Chong, Brian Skaug, Zhijian J. Chen, George E. Davis, Ondine Cleaver

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)526-539
Number of pages14
JournalDevelopmental Cell
Volume20
Issue number4
DOIs
StatePublished - Apr 19 2011

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GTP Phosphohydrolases
Blood vessels
Blood Vessels
Endothelial cells
Adhesion
Myosin Type II
Extracellular Matrix
rho GTP-Binding Proteins
Endothelial Cells
Integrins
ras Proteins
Cell Polarity
Cytoskeleton
Morphogenesis
Cultured Cells
Defects
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Blood Vessel Tubulogenesis Requires Rasip1 Regulation of GTPase Signaling. / Xu, Ke; Sacharidou, Anastasia; Fu, Stephen; Chong, Diana C.; Skaug, Brian; Chen, Zhijian J.; Davis, George E.; Cleaver, Ondine.

In: Developmental Cell, Vol. 20, No. 4, 19.04.2011, p. 526-539.

Research output: Contribution to journalArticle

Xu, Ke ; Sacharidou, Anastasia ; Fu, Stephen ; Chong, Diana C. ; Skaug, Brian ; Chen, Zhijian J. ; Davis, George E. ; Cleaver, Ondine. / Blood Vessel Tubulogenesis Requires Rasip1 Regulation of GTPase Signaling. In: Developmental Cell. 2011 ; Vol. 20, No. 4. pp. 526-539.
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