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@ARTICLE{Roth:130443,
author = {L. Roth$^*$ and C. Prahst$^*$ and T. Ruckdeschel$^*$ and S.
Savant$^*$ and S. Weström$^*$ and A. Fantin and M.
Riedel$^*$ and M. Héroult$^*$ and C. Ruhrberg and H.
Augustin$^*$},
title = {{N}europilin-1 mediates vascular permeability independently
of vascular endothelial growth factor receptor-2
activation.},
journal = {Science signaling},
volume = {9},
number = {425},
issn = {1937-9145},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DKFZ-2017-05522},
pages = {ra42 - ra42},
year = {2016},
abstract = {Neuropilin-1 (NRP1) regulates developmental and
pathological angiogenesis, arteriogenesis, and vascular
permeability, acting as a coreceptor for semaphorin 3A
(Sema3A) and the 165-amino acid isoform of vascular
endothelial growth factor A (VEGF-A165). NRP1 is also the
receptor for the CendR peptides, a class of cell- and
tissue-penetrating peptides with a specific R-x-x-R
carboxyl-terminal motif. Because the cytoplasmic domain of
NRP1 lacks catalytic activity, NRP1 is mainly thought to act
through the recruitment and binding to other receptors. We
report here that the NRP1 intracellular domain mediates
vascular permeability. Stimulation with VEGF-A165, a
ligand-blocking antibody, and a CendR peptide led to NRP1
accumulation at cell-cell contacts in endothelial cell
monolayers, increased cellular permeability in vitro and
vascular leakage in vivo. Biochemical analyses, VEGF
receptor-2 (VEGFR-2) silencing, and the use of a specific
VEGFR blocker established that the effects induced by the
CendR peptide and the antibody were independent of VEGFR-2.
Moreover, leakage assays in mice expressing a mutant NRP1
lacking the cytoplasmic domain revealed that this domain was
required for NRP1-induced vascular permeability in vivo.
Hence, these data define a vascular permeability pathway
mediated by NRP1 but independent of VEGFR-2 activation.},
cin = {A190},
ddc = {500},
cid = {I:(DE-He78)A190-20160331},
pnm = {321 - Basic Concepts (POF3-321)},
pid = {G:(DE-HGF)POF3-321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27117252},
doi = {10.1126/scisignal.aad3812},
url = {https://inrepo02.dkfz.de/record/130443},
}