| First Author | Le Guelte A | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 17 | Pages | 4137-46 |
| PubMed ID | 22685328 | Mgi Jnum | J:198888 |
| Mgi Id | MGI:5499701 | Doi | 10.1242/jcs.108282 |
| Citation | Le Guelte A, et al. (2012) Semaphorin 3A elevates endothelial cell permeability through PP2A inactivation. J Cell Sci 125(Pt 17):4137-46 |
| abstractText | VE-cadherin-mediated cell-cell junction weakening increases paracellular permeability in response to both angiogenic and inflammatory stimuli. Although Semaphorin 3A has emerged as one of the few known anti-angiogenic factors to exhibit pro-permeability activity, little is known about how it triggers vascular leakage. Here we report that Semaphorin 3A induced VE-cadherin serine phosphorylation and internalisation, cell-cell junction destabilisation, and loss of barrier integrity in brain endothelial cells. In addition, high-grade glioma-isolated tumour-initiating cells were found to secrete Semaphorin 3A, which promoted brain endothelial monolayer permeability. From a mechanistic standpoint, Semaphorin 3A impinged upon the basal activity of the serine phosphatase PP2A and disrupted PP2A interaction with VE-cadherin, leading to cell-cell junction disorganization and increased permeability. Accordingly, both pharmacological inhibition and siRNA-based knockdown of PP2A mimicked Semaphorin 3A effects on VE-cadherin. Hence, local Semaphorin 3A production impacts on the PP2A/VE-cadherin equilibrium and contributes to elevated vascular permeability. |
