AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties.
Blood
; 117(2): 708-18, 2011 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-20952690
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adesão Celular
/
Fatores de Troca do Nucleotídeo Guanina
/
Proteínas do Citoesqueleto
/
Células Endoteliais
/
Proteínas de Ancoragem à Quinase A
/
Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos