期刊
JOURNAL OF CELL SCIENCE
卷 134, 期 24, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.259012
关键词
Cadherin; Mechanobiology; Cell adhesion; Endothelial cell junctions; Vascular biology
类别
资金
- Max Planck Society (Max-PlanckGesellschaft)
- CIM-IMPRS graduate school (University of Munster)
- Deutsche Forschungsgemeinschaft [SFB1348]
- Max-Planck-Gesellschaft
Cadherin-mediated cell adhesion relies on anchoring to the actin cytoskeleton via the beta-catenin-alpha-catenin complex. Fusion of VE-cadherin to alpha-catenin enhances this anchorage in endothelial cells, leading to stabilized endothelial junctions. The mechanism involves constitutive recruitment of vinculin by VE-cadherin-alpha-catenin, as well as conformational changes in the actin-binding domain of alpha-catenin.
Cadherin-mediated cell adhesion requires anchoring via the beta-catenin-alpha-catenin complex to the actin cytoskeleton, yet, alpha-catenin only binds F-actin weakly. A covalent fusion of VE-cadherin to alpha-catenin enhances actin anchorage in endothelial cells and strongly stabilizes endothelial junctions in vivo, blocking inflammatory responses. Here, we have analyzed the underlying mechanism. We found that VE-cadherin-alpha-catenin constitutively recruits the actin adaptor vinculin. However, removal of the vinculin-binding region of alpha-catenin did not impair the ability of VE-cadherin-alpha-catenin to enhance junction integrity. Searching for an alternative explanation for the junction-stabilizing mechanism, we found that an antibody-defined epitope, normally buried in a short alpha 1-helix of the actin-binding domain (ABD) of alpha-catenin, is openly displayed in junctional VE-cadherin-alpha-catenin chimera. We found that this epitope became exposed in normal alpha-catenin upon triggering thrombin-induced tension across the VE-cadherin complex. These results suggest that the VE-cadherin-alpha-catenin chimera stabilizes endothelial junctions due to conformational changes in the ABD of alpha-catenin that support constitutive strong binding to actin.
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