Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin. J Exp Med 2014 Mar 10;211(3):579-91
Date
03/05/2014Pubmed ID
24590762Pubmed Central ID
PMC3949568DOI
10.1084/jem.20131190Scopus ID
2-s2.0-84896846354 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Gong H, Gao X, Feng S, Siddiqui MR, Garcia A, Bonini MG, Komarova Y, Vogel SM, Mehta D, Malik ABMESH terms used to index this publication - Major topics in bold
Adherens JunctionsAnimals
Antigens, CD
Biotinylation
Blotting, Western
Cadherins
Electric Impedance
Endocytosis
Endothelial Cells
Evans Blue
GTP-Binding Protein alpha Subunits, G12-G13
Genes, src
Hydrogen Peroxide
Immunoprecipitation
Inflammation
Mice
Mice, Knockout
Permeability
Phosphorylation
RNA Interference
