N‐cadherin Signaling via RhoGEF Trio Stabilizes VE‐cadherin Junctions and Regulates Vascular Permeability

Capillary endothelial cells express Vascular Endothelial (VE)‐ and Neural (N)‐cadherin, with overlapping functions. VE‐cadherin forms homotypic adhesion between endothelial cells whereas N‐cadherin forms heterotypic adhesion with the surrounding pericytes in capillary endothelia. Endothelial specific deletions of Cdh2 (N‐cadherin) or Cdh5 (VE‐cadherin) in mice demonstrated poorly formed leaky capillaries and in utero death at E9.5 due to defective angiogenesis. These findings raise the question of whether N‐ and VE‐cadherin function independently or whether N‐cadherin activated signaling regulates the assembly of VE‐cadherin and thereby the formation of adherens junctions. We investigated the role of N‐cadherin in the formation of VE‐cadherin junctions using mouse genetic models and identifying N‐cadherin signaling pathways in endothelial monolayers. We show that N‐cadherin functions by interacting with the RhoGEF Trio to activate the RhoGTPases Rac1 and RhoA in nascent adherens junctions, inducing the recruitment of VE‐cadherin. This N‐cadherin activated signaling pathway is essential for maximal VE‐cadherin assembly and the formation of the endothelial junctional barrier. Support or Funding Information Supported by NIH grant R01 HL103922 to Y.A.K.; AHA AWARD 16PRE27260230 to K.K. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .