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Updated: May 12, 2026

Lineage-reprogramming of Pericyte-derived Cells of the Adult Human Brain into Induced Neurons
Published on: May 13, 2014
Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial
S Soker1, S Takashima, H Q Miao
1Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, binds to two receptor tyrosine kinases, KDR/Flk-1 and Flt-1. We now describe the purification and the expression cloning from tumor cells of a third VEGF receptor, one that binds VEGF165 but not VEGF121. This isoform-specific VEGF receptor (VEGF165R) is identical to human neuropilin-1, a receptor for the collapsin/semaphorin family that mediates neuronal cell guidance. When coexpressed in cells with KDR, neuropilin-1 enhances the binding of VEGF165 to KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to neuropilin-1 inhibits its binding to KDR and its mitogenic activity for endothelial cells. We propose that neuropilin-1 is a novel VEGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and therefore may regulate VEGF-induced angiogenesis.
Insights
Neuropilin-1 acts as a third vascular endothelial growth factor (VEGF) receptor, specifically binding VEGF165. This interaction enhances VEGF165 binding to KDR, modulating angiogenesis and endothelial cell activity.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Vascular endothelial growth factor (VEGF) is crucial for angiogenesis, primarily signaling through KDR/Flk-1 and Flt-1 receptors.
- Tumor cells express various growth factor receptors, influencing tumor growth and metastasis.
Purpose of the Study:
- To identify and characterize novel receptors for VEGF.
- To investigate the role of a newly identified VEGF receptor in angiogenesis.
Main Methods:
- Purification and expression cloning of a novel VEGF receptor from tumor cells.
- Coexpression studies with KDR to assess binding and functional activity.
- Inhibition assays to determine the role of neuropilin-1 in VEGF signaling.
Main Results:
- A third VEGF receptor, binding VEGF165 but not VEGF121, was identified and cloned.
- This receptor was found to be identical to human neuropilin-1.
- Neuropilin-1 enhanced VEGF165 binding to KDR and VEGF165-mediated chemotaxis.
- Inhibiting neuropilin-1 binding reduced VEGF165's mitogenic activity on endothelial cells.
Conclusions:
- Neuropilin-1 functions as a novel VEGF receptor, modulating VEGF165 binding to KDR.
- Neuropilin-1 plays a significant role in regulating VEGF-induced angiogenesis and endothelial cell function.
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