Unknown

Dataset Information

0

AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties.


ABSTRACT: Adhesive forces at endothelial cell-cell borders maintain vascular integrity. cAMP enhances barrier properties and controls cellular processes through protein kinase A bound to A-kinase anchoring proteins (AKAPs). It also activates exchange protein directly activated by cAMP (Epac1), an exchange factor for Ras-related protein 1 (Rap1) GTPases that promotes cadherin- and integrin-mediated adhesion through effects on the actin cytoskeleton. We demonstrate that AKAP9 facilitates the microtubule polymerization rate in endothelial cells, interacts with Epac1, and is required for Epac1-stimulated microtubule growth. AKAP9 is not required for maintaining barrier properties under steady-state conditions. Rather, it is essential when the cell is challenged to make new adhesive contacts, as is the case when Epac activation enhances barrier function through a mechanism that, surprisingly, requires integrin adhesion at cell-cell contacts. In the present study, defects in Epac-induced responses in AKAP9-silenced cells were evident despite an intact Epac-induced increase in Rap activation, cortical actin, and vascular endothelial-cadherin adhesion. We describe a pathway that integrates Epac-mediated signals with AKAP9-dependent microtubule dynamics to coordinate integrins at lateral borders.

SUBMITTER: Sehrawat S 

PROVIDER: S-EPMC3031489 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC2262967 | BioStudies
2017-01-01 | S-EPMC5256679 | BioStudies
| S-EPMC2820423 | BioStudies
2020-01-01 | S-EPMC7601253 | BioStudies
| S-EPMC3845138 | BioStudies
2019-01-01 | S-EPMC6855264 | BioStudies
1000-01-01 | S-EPMC3081154 | BioStudies
| S-EPMC3627495 | BioStudies
2016-01-01 | S-EPMC4742228 | BioStudies
2014-01-01 | S-EPMC4179905 | BioStudies