Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 21, Issue 4, Pages 584-596Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E09-07-0580
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Funding
- Ministry of Education, Science, Sports and Culture of Japan
- Ministry of Health, Labor, and Welfare of Japan
- National Institute of Biomedical Innovation
- Naito Foundation
- Takeda Science Foundation
- Sagawa Foundation for Promotion of Cancer Research
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kowa Life Science Foundation
- Kanae Foundation
- Novartis Foundation (Japan) for the Promotion of Science
- Senri Life Science Foundation
- Mitsubishi Foundation
- AstraZeneca
- Grants-in-Aid for Scientific Research [22390040] Funding Source: KAKEN
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Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-catenin, and beta-catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of alpha- and beta-catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that alpha-catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.
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