N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability

DOI PDF 被引用文献1件
  • Kevin Kruse
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Quinn S. Lee
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Ying Sun
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Jeff Klomp
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Xiaoyan Yang
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Fei Huang
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Mitchell Y. Sun
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Shuangping Zhao
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Zhigang Hong
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Stephen M. Vogel
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Jae-Won Shin
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Deborah E. Leckband
    Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana–Champaign, Urbana, IL 3
  • Leon M. Tai
    Department of Anatomy and Cell Biology, University of Illinois College of Medicine, Chicago, IL 2
  • Asrar B. Malik
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1
  • Yulia A. Komarova
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 1

説明

<jats:p>Vascular endothelial (VE)–cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin (Cdh2) in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs. N-cadherin functions by increasing the rate of VE-cadherin recruitment to AJs and induces the assembly of VE-cadherin junctions. We identified the dual Rac1/RhoA Rho guanine nucleotide exchange factor (GEF) Trio as a critical component of the N-cadherin adhesion complex, which activates both Rac1 and RhoA signaling pathways at AJs. Trio GEF1-mediated Rac1 activation induces the recruitment of VE-cadherin to AJs, whereas Trio GEF2-mediated RhoA activation increases intracellular tension and reinforces Rac1 activation to promote assembly of VE-cadherin junctions and thereby establish the characteristic restrictive endothelial barrier.</jats:p>

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