Unknown

Dataset Information

0

Local VE-cadherin mechanotransduction triggers long-ranged remodeling of endothelial monolayers.


ABSTRACT: In this study, we present results demonstrating that mechanotransduction by vascular endothelial cadherin (VE-cadherin, also known as CDH5) complexes in endothelial cells triggers local cytoskeletal remodeling, and also activates global signals that alter peripheral intercellular junctions and disrupt cell-cell contacts far from the site of force application. Prior studies have documented the impact of actomyosin contractile forces on adherens junction remodeling, but the role of VE-cadherin in force sensation and its ability to influence endothelial cell and tissue mechanics globally have not been demonstrated. Using mechanical manipulation of VE-cadherin bonds and confocal imaging, we demonstrate VE-cadherin-based mechanotransduction. We then demonstrate that it requires homophilic VE-cadherin ligation, an intact actomyosin cytoskeleton, Rho-associated protein kinase 1 (ROCK1) and phosphoinositide 3-kinase. VE-cadherin-mediated mechanotransduction triggered local actin and vinculin recruitment, as well as global signals that altered focal adhesions and disrupted peripheral intercellular junctions. Confocal imaging revealed that VE-cadherin-specific changes appear to propagate across cell junctions to disrupt distant inter-endothelial junctions. These results demonstrate the central role of VE-cadherin adhesions and the actomyosin cytoskeleton within an integrated, mechanosensitive network that both induces local cytoskeletal remodeling at the site of force application and regulates the global integrity of endothelial tissues.

SUBMITTER: Barry AK 

PROVIDER: S-EPMC4379726 | BioStudies | 2015-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5757379 | BioStudies
| S-EPMC6625547 | BioStudies
| S-EPMC4362456 | BioStudies
2018-01-01 | S-EPMC5940301 | BioStudies
2018-03-05 | S-JCBD-201708103 | BioStudies
1000-01-01 | S-EPMC4284224 | BioStudies
| S-EPMC5667920 | BioStudies
1000-01-01 | S-EPMC4150062 | BioStudies
2021-07-27 | S-SCDT-EMBOJ-2020-106113 | BioStudies
2014-01-01 | S-EPMC3890345 | BioStudies