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Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility

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Miao, Hua-Quan, Soker, Shay, Feiner, Leonard, Alonso, José Luis, Raper, Jonathan A., Klagsbrun, Michael·1999·The Journal of Cell Biology

Abstract

Neuropilin-1 (NRP1) is a receptor for two unrelated ligands with disparate activities, vascular endothelial growth factor-165 (VEGF165), an angiogenesis factor, and semaphorin/collapsins, mediators of neuronal guidance. To determine whether semaphorin/collapsins could interact with NRP1 in nonneuronal cells, the effects of recombinant collapsin-1 on endothelial cells (EC) were examined. Collapsin-1 inhibited the motility of porcine aortic EC (PAEC) expressing NRP1 alone; coexpressing KDR and NRP1 (PAEC/KDR/NRP1), but not parental PAEC; or PAEC expressing KDR alone. The motility of PAEC expressing NRP1 was inhibited by 65–75% and this inhibition was abrogated by anti-NRP1 antibody. In contrast, VEGF165 stimulated the motility of PAEC/KDR/NRP1. When VEGF165 and collapsin-1 were added simultaneously to PAEC/KDR/NRP1, dorsal root ganglia (DRG), and COS-7/NRP1 cells, they competed with each other in EC motility, DRG collapse, and NRP1-binding assays, respectively, suggesting that the two ligands have overlapping NRP1 binding sites. Collapsin-1 rapidly disrupted the formation of lamellipodia and induced depolymerization of F-actin in an NRP1-dependent manner. In an in vitro angiogenesis assay, collapsin-1 inhibited the capillary sprouting of EC from rat aortic ring segments. These results suggest that collapsin-1 can inhibit EC motility as well as axon motility, that these inhibitory effects on motility are mediated by NRP1, and that VEGF165 and collapsin-1 compete for NRP1-binding sites.

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Metadata

Authors
Miao, H.-Q., Soker, S., Feiner, L., Alonso, J. L., Raper, J. A., & Klagsbrun, M.
Venue
The Journal of Cell Biology
Published
1999-07-12
Volume
146
Issue
1
Pages
233-242
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W1998413748
Cited by
458
References
0
FWCI
8.71
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility. https://app.cochat.ai/papers/10.1083/jcb.146.1.233
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Miao, H.-Q., Soker, S., Feiner, L., Alonso, J. L., Raper, J. A., & Klagsbrun, M. (1999). Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility. The Journal of Cell Biology. https://doi.org/10.1083/jcb.146.1.233

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