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Vascular Endothelial Growth Factor and Semaphorin Induce Neuropilin-1 Endocytosis via Separate Pathways
Abstract
The neuropilin (Nrp)1 receptor is essential for both nervous and vascular system development. Nrp1 is unusually versatile, because it transmits both chemoattractive and repulsive signals in response to vascular endothelial growth factor (VEGF)-A and class 3 semaphorins, respectively. Both Nrp1 and VEGF receptor 2 undergo ligand-dependent endocytosis. We sought to establish the endocytic pathway of Nrp1 and to determine whether uptake is required for its signaling. Whereas Nrp1 underwent clathrin-dependent endocytosis in response to VEGFA 165 treatment, semaphorin 3C (sema3C) induced lipid raft–dependent endocytosis. The myosin VI PDZ (postsynaptic density 95, Disk large, Zona occludens-1) adaptor protein synectin was essential for Nrp1 trafficking. Sema3C failed to inhibit migration of synectin −/− endothelial cells, mirroring the lower migratory response of these cells to VEGFA 165 . These results show that the endocytic pathway of Nrp1 is determined by its ligand and that the trafficking of Nrp1 is essential for its signaling.
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Several DEGs previously associated with lipid metabolism were identified, including MIAT, COMT, NRP1, VEGFB, GRAMD1B, DSEL, and FUT9 associated with glycan structure.
“We identified several DEGs that have been previously associated with lipid metabolism, including MIAT, COMT, NRP1, VEGFB, GRAMD1B, DSEL56–62, as well as FUT9 associated with glycan structure63,64 (Fig. 4a).”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [61]
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Metadata
- Authors
- Salikhova, A., Wang, L., Lanahan, A. A., Liu, M., Simons, M., Leenders, W. P. J., Mukhopadhyay, D., & Horowitz, A.
- Affiliations
- From the Angiogenesis Research Center (A.S., A.A.L., M.L., M.S., A.H.), Dartmouth Medical School, Lebanon, NH; Department of Biochemistry and Molecular Biology (L.W., D.M.), Mayo Clinic Cancer Center, Rochester, Minn; and Department of Pathology (W.P.J.L.), Radboud University, Nijmegen Medical Centre, The Netherlands.
- Venue
- Circulation Research
- Published
- 2008-09-12
- Volume
- 103
- Issue
- 6
- ISSN
- 0009-7330
- 1524-4571
- PMC
- PMC2674948
- Cited by
- 105
- References
- 0
- Language
- en
- Update notices
- correction (2010-10-29)
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