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

J Biochem. 2017 Jul 1;162(1):55-62. doi: 10.1093/jb/mvx001.

Abstract

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.

Keywords: VE-PTP; VE-cadherin; VEGF; plakoglobin; vascular endothelial cells.

MeSH terms

  • Antigens, CD / metabolism*
  • Cadherins / metabolism*
  • Endothelial Cells / metabolism*
  • Humans
  • Intercellular Junctions / metabolism*
  • Phosphorylation
  • Signal Transduction
  • Vascular Endothelial Growth Factors / metabolism*
  • gamma Catenin / metabolism*

Substances

  • Antigens, CD
  • Cadherins
  • Vascular Endothelial Growth Factors
  • cadherin 5
  • gamma Catenin