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Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2014 Mar 10; Vol. 211 (3), pp. 579-91. Date of Electronic Publication: 2014 Mar 03. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Biotinylation
Blotting, Western
Electric Impedance
Endocytosis physiology
Endothelial Cells cytology
Evans Blue
GTP-Binding Protein alpha Subunits, G12-G13 deficiency
Genes, src genetics
Hydrogen Peroxide metabolism
Immunoprecipitation
Mice
Mice, Knockout
Permeability
Phosphorylation
RNA Interference
Adherens Junctions metabolism
Antigens, CD metabolism
Cadherins metabolism
Endothelial Cells metabolism
GTP-Binding Protein alpha Subunits, G12-G13 metabolism
Inflammation metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 211
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24590762
- Full Text :
- https://doi.org/10.1084/jem.20131190