Role of N-cadherin Adhesion Mediated Signaling in Regulating Stability of VE-cadherin Adhesions Role of N-cadherin Adhesion Mediated Signaling in Regulating Stability of VE-cadherin Adhesions and Permeability Endothelial Barrier Function
Session Number
C28
Advisor(s)
Yulia Komarova, University of Illinois at Chicago Kevin Kruse, University of Illinois at Chicago Asrar Malik, University of Illinois at Chicago
Location
B-125 Tellabs
Start Date
28-4-2016 11:05 AM
End Date
28-4-2016 11:30 AM
Abstract
The endothelial monolayer lining the vascular system maintains tissue-fluid homeostasis through selective permeability. This permeability is a result of inter-endothelial junctions such as adherens junctions (AJs), which provide a physical attachment of endothelial cells by extracellular Vascular- Endothelial (VE)-cadherin adhesion. Stability of AJs is regulated by anchorage of VE-cadherin complexes of associated alpha-, beta-, and p120-catenins to the actin cytoskeleton in the Rho GTPasedependent manner. Neural (N)-cadherin form adhesion between endothelial and mural cells. Recent studies suggest that N-cadherin might also regulate endothelial barrier permeability. However, the complete mechanism of N-cadherin and VE-cadherin cross-interactions remains unknown. Data from the lab suggest that N-cadherin might control activity of RhoGTPases at AJs. Rho GTPases are molecular switches cycling between GTP- and GDP-bound states. This process is activated and inhibited by guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins. Trio is a RhoGEF consisting of two GEF domains. GEF1 activates Rac1 and RhoG while GEF2 activates RhoA. Trio needs Neuron Navigator (NAV)1 to activate Rac1. In this study, we investigated effect of NAV1 and Ncadherin signaling on recruitment of VE-cadherin to AJs. Our data show that both proteins are required for stabilization of VE-cadherin adhesion and restricting permeability.
Role of N-cadherin Adhesion Mediated Signaling in Regulating Stability of VE-cadherin Adhesions Role of N-cadherin Adhesion Mediated Signaling in Regulating Stability of VE-cadherin Adhesions and Permeability Endothelial Barrier Function
B-125 Tellabs
The endothelial monolayer lining the vascular system maintains tissue-fluid homeostasis through selective permeability. This permeability is a result of inter-endothelial junctions such as adherens junctions (AJs), which provide a physical attachment of endothelial cells by extracellular Vascular- Endothelial (VE)-cadherin adhesion. Stability of AJs is regulated by anchorage of VE-cadherin complexes of associated alpha-, beta-, and p120-catenins to the actin cytoskeleton in the Rho GTPasedependent manner. Neural (N)-cadherin form adhesion between endothelial and mural cells. Recent studies suggest that N-cadherin might also regulate endothelial barrier permeability. However, the complete mechanism of N-cadherin and VE-cadherin cross-interactions remains unknown. Data from the lab suggest that N-cadherin might control activity of RhoGTPases at AJs. Rho GTPases are molecular switches cycling between GTP- and GDP-bound states. This process is activated and inhibited by guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins. Trio is a RhoGEF consisting of two GEF domains. GEF1 activates Rac1 and RhoG while GEF2 activates RhoA. Trio needs Neuron Navigator (NAV)1 to activate Rac1. In this study, we investigated effect of NAV1 and Ncadherin signaling on recruitment of VE-cadherin to AJs. Our data show that both proteins are required for stabilization of VE-cadherin adhesion and restricting permeability.