Neuropilin-1 mediates vascular permeability independently of vascular endothelial growth factor receptor-2 activation

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Science Signaling  26 Apr 2016:
Vol. 9, Issue 425, pp. ra42
DOI: 10.1126/scisignal.aad3812

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Multiple paths to leaky blood vessels

The endothelial cells that line blood vessels act as a barrier between the blood and many tissues in the body. Blood vessels that are excessively leaky can lead to fluid buildup in tissues and promote the inappropriate movement of cells, such as the metastasis of cancer cells into the blood. The binding of VEGF (vascular endothelial cell growth factor) to its receptor VEGFR-2 enhances vascular permeability. Roth et al. discovered that different ligands that bound and triggered the clustering of VEGF coreceptor NRP1 increased vascular permeability without involving VEGFR-2 activation. In mice that expressed a form of NRP1 lacking the cytoplasmic domain, the NRP1-clustering stimuli did not enhance leakage from blood vessels. Thus, understanding how the cytoplasmic domain of NRP1 mediates increased vascular permeability may lead to new targets for preventing this condition.