title: Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin.
abstract: The heterotrimeric G protein Gα13 transduces signals from G protein-coupled receptors (GPCRs) to induce cell spreading, differentiation, migration, and cell polarity. Here, we describe a novel GPCR-independent function of Gα13 in regulating the stability of endothelial cell adherens junctions (AJs). We observed that the oxidant H2O2, which is released in response to multiple proinflammatory mediators, induced the interaction of Gα13 with VE-cadherin. Gα13 binding to VE-cadherin in turn induced Src activation and VE-cadherin phosphorylation at Tyr 658, the p120-catenin binding site thought to be responsible for VE-cadherin internalization. Inhibition of Gα13-VE-cadherin interaction using an interfering peptide derived from the Gα13 binding motif on VE-cadherin abrogated the disruption of AJs in response to inflammatory mediators. These studies identify a unique role of Gα13 binding to VE-cadherin in mediating VE-cadherin internalization and endothelial barrier disruption and inflammation.
authors.affiliation: Department of Pharmacology and the Center for Lung and Vascular Biology, University of Illinois, Chicago, Il 60612.
authors.forename: Haixia
authors.initials: H
authors.lastname: Gong
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Gao
authors.forename: Shaoting
authors.initials: S
authors.lastname: Feng
authors.forename: M Rizwan
authors.initials: MR
authors.lastname: Siddiqui
authors.forename: Alexander
authors.initials: A
authors.lastname: Garcia
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Bonini
authors.forename: Yulia
authors.initials: Y
authors.lastname: Komarova
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vogel
authors.forename: Dolly
authors.initials: D
authors.lastname: Mehta
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D019921:Biotinylation; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D017097:Electric Impedance; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005070:Evans Blue; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency / Q000378:metabolism*; D016391:Genes, src / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D047468:Immunoprecipitation; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D010766:Phosphorylation; D034622:RNA Interference; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D005070:Evans Blue; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D006861:Hydrogen Peroxide; D000099152:Cadherin 5