Plakoglobin maintains the integrity of vascular endothelial cell junctions and regulates VEGF-induced phosphorylation of VE-cadherin.
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.
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Fumitaka
F
Muramatsu
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Hiroyasu
H
Kidoya
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Hisamichi
H
Naito
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Yumiko
Y
Hayashi
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Tomohiro
T
Iba
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan.
Nobuyuki
N
Takakura
D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D042442:Vascular Endothelial Growth Factors; D051185:gamma Catenin; D000099152:Cadherin 5
VE-PTP; VE-cadherin; VEGF; plakoglobin; vascular endothelial cells