Plakoglobin maintains the integrity of vascular endothelial cell junctions and regulates VEGF-induced phosphorylation of VE-cadherin

• Published in: Journal of biochemistry (Tokyo) 2017-07, Vol.162 (1), p.55-62
• Main Authors: Muramatsu, Fumitaka, Kidoya, Hiroyasu, Naito, Hisamichi, Hayashi, Yumiko, Iba, Tomohiro, Takakura, Nobuyuki
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Cadherins - metabolism; Endothelial Cells - metabolism; gamma Catenin - metabolism; Humans; Intercellular Junctions - metabolism; Phosphorylation; Signal Transduction; Vascular Endothelial Growth Factors - metabolism
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvx001

Plakoglobin, also known as γ-catenin, is a close homolog of β-catenin and interacts with shared protein partners. Functions of β-catenin in cell adhesion are well-documented in terms of maintaining endothelial barrier function by interacting with vascular endothelial (VE)-cadherin. Plakoglobin also interacts with VE-cadherin, but its function in cell adhesion is not well understood. Here, we investigated plakoglobin function in vascular endothelial cell (ECs)-cell junction integrity. Knock-down of plakoglobin expression in ECs did not prevent cell proliferation or cell migration, but induced destabilization of the membrane distribution of VE-cadherin and resulted in increased permeability. Plakoglobin contributes to VE-cadherin-dependent adhesion in the steady state, but on stimulation with vascular endothelial growth factor (VEGF), it is essential for inducing sufficient VE-cadherin phosphorylation on VEGF signaling, thereby destabilizing cell-cell junctions. Furthermore, knock-down of plakoglobin expression increased vascular endothelial protein tyrosine phosphatase activity, an endothelial-specific membrane protein associating with VE-cadherin. These results indicate that plakoglobin plays multiple roles in regulation of cell-cell adhesion in a context dependent manner.