Plakoglobin does not participate in endothelial barrier stabilization mediated by cAMP

Hamad, Ibrahim; Sepic, Sara; Moztarzadeh, Sina; García-Ponce, Alexander; Waschke, Jens; Radeva, Mariya Y. (2025): Plakoglobin does not participate in endothelial barrier stabilization mediated by cAMP. Scientific Reports, 15: 9043. ISSN 2045-2322

Abstract

Critical for maintenance of endothelial barrier is the remodeling of the actin cytoskeleton and the precise control of junctional integrity. Plakoglobin (PG) is a structural and signaling protein involved in vascular permeability regulation together with key signaling molecules such as cAMP, Rho GTPases and actin-binding proteins. Here, we investigated the role of PG in cAMP-mediated endothelial barrier stabilization by establishing myocardial endothelial cells derived from wild type (WT) and PG knock-out (PG-KO) mice. Under basal conditions, TEER measurements showed increased barrier function of PG-KO, an effect associated with enhanced protein levels and junctional VE-cadherin and β-catenin accumulation. PG-KO cells also displayed more PECAM-1 and VE-PTP-phosphatase and less phosphorylated VE-cadherin, typically linked with modulation of junctional integrity. PG ablation neither changed the composition of VE-cadherin/β-catenin complex nor activities of Rac1 and RhoA but decreased the basal intracellular cAMP concentration. Remarkably, cAMP augmentation led to enhanced Rac1 activity and TEER in both cell lines, but the effect was less prominent in PG-KO. The tighter barrier in WT was paralleled with more VE-cadherin, β-catenin and cortactin, an actin-binding protein, towards junctions. Surprisingly, PG phosphorylation at Ser665 was not required for cAMP-mediated endothelial barrier integrity, which is different to cardiomyocyte and keratinocyte cell adhesion.

• Dokumententyp: Artikel (LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Anatomische Anstalt
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892