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N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier

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posted on 28.11.2018 by Kevin Jonathan Kruse
Endothelial cells express Vascular Endothelial (VE)- and Neural (N)-cadherin, which have 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. I investigated the role of N-cadherin in the formation of VE-cadherin junctions using mouse genetic models and identified N-cadherin a novel signaling pathway in endothelial cells. I show that N-cadherin functions by interacting with the RhoGEF Trio to activate the RhoGTPases Rac1 and RhoA at 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.

History

Advisor

Komarova, Yulia

Chair

Komarova, Yulia

Department

Pharmacology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Mehta, Dolly Levitan, Irena Shin, Jae-Won Tai, Leon

Submitted date

August 2018

Issue date

22/06/2018

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