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Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165
Neuropilin-1 (NRP1) is a receptor for two unrelated ligands with disparate activities, vascular endothelial growth factor-165 (VEGF(165)), an angiogenesis factor, and semaphorin/collapsins, mediators of neuronal guidance. To determine whether semaphorin/collapsins could interact with NRP1 in nonneur...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199727/ https://www.ncbi.nlm.nih.gov/pubmed/10402473 |
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author | Miao, Hua-Quan Soker, Shay Feiner, Leonard Alonso, José Luis Raper, Jonathan A. Klagsbrun, Michael |
author_facet | Miao, Hua-Quan Soker, Shay Feiner, Leonard Alonso, José Luis Raper, Jonathan A. Klagsbrun, Michael |
author_sort | Miao, Hua-Quan |
collection | PubMed |
description | Neuropilin-1 (NRP1) is a receptor for two unrelated ligands with disparate activities, vascular endothelial growth factor-165 (VEGF(165)), 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, VEGF(165) stimulated the motility of PAEC/KDR/NRP1. When VEGF(165) 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 VEGF(165) and collapsin-1 compete for NRP1-binding sites. |
format | Text |
id | pubmed-2199727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21997272008-05-01 Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 Miao, Hua-Quan Soker, Shay Feiner, Leonard Alonso, José Luis Raper, Jonathan A. Klagsbrun, Michael J Cell Biol Original Article Neuropilin-1 (NRP1) is a receptor for two unrelated ligands with disparate activities, vascular endothelial growth factor-165 (VEGF(165)), 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, VEGF(165) stimulated the motility of PAEC/KDR/NRP1. When VEGF(165) 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 VEGF(165) and collapsin-1 compete for NRP1-binding sites. The Rockefeller University Press 1999-07-12 /pmc/articles/PMC2199727/ /pubmed/10402473 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Miao, Hua-Quan Soker, Shay Feiner, Leonard Alonso, José Luis Raper, Jonathan A. Klagsbrun, Michael Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title | Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title_full | Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title_fullStr | Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title_full_unstemmed | Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title_short | Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 |
title_sort | neuropilin-1 mediates collapsin-1/semaphorin iii inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199727/ https://www.ncbi.nlm.nih.gov/pubmed/10402473 |
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