| First Author | Juettner VV | Year | 2019 |
| Journal | J Cell Biol | Volume | 218 |
| Issue | 5 | Pages | 1725-1742 |
| PubMed ID | 30948425 | Mgi Jnum | J:274903 |
| Mgi Id | MGI:6296875 | Doi | 10.1083/jcb.201807210 |
| Citation | Juettner VV, et al. (2019) VE-PTP stabilizes VE-cadherin junctions and the endothelial barrier via a phosphatase-independent mechanism. J Cell Biol 218(5):1725-1742 |
| abstractText | Vascular endothelial (VE) protein tyrosine phosphatase (PTP) is an endothelial-specific phosphatase that stabilizes VE-cadherin junctions. Although studies have focused on the role of VE-PTP in dephosphorylating VE-cadherin in the activated endothelium, little is known of VE-PTP's role in the quiescent endothelial monolayer. Here, we used the photoconvertible fluorescent protein VE-cadherin-Dendra2 to monitor VE-cadherin dynamics at adherens junctions (AJs) in confluent endothelial monolayers. We discovered that VE-PTP stabilizes VE-cadherin junctions by reducing the rate of VE-cadherin internalization independently of its phosphatase activity. VE-PTP serves as an adaptor protein that through binding and inhibiting the RhoGEF GEF-H1 modulates RhoA activity and tension across VE-cadherin junctions. Overexpression of the VE-PTP cytosolic domain mutant interacting with GEF-H1 in VE-PTP-depleted endothelial cells reduced GEF-H1 activity and restored VE-cadherin dynamics at AJs. Thus, VE-PTP stabilizes VE-cadherin junctions and restricts endothelial permeability by inhibiting GEF-H1, thereby limiting RhoA signaling at AJs and reducing the VE-cadherin internalization rate. |
