Vascular endothelial growth factor and semaphorin induce neuropilin-1 endocytosis via separate pathways. Circ Res 2008 Sep 12;103(6):e71-9
Date
08/30/2008Pubmed ID
18723443Pubmed Central ID
PMC2674948DOI
10.1161/CIRCRESAHA.108.183327Scopus ID
2-s2.0-53249096017 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
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.
Author List
Salikhova A, Wang L, Lanahan AA, Liu M, Simons M, Leenders WP, Mukhopadhyay D, Horowitz AMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Carrier Proteins
Cells, Cultured
Chickens
Clathrin
Endocytosis
Humans
Ligands
Membrane Microdomains
Mice
Mice, Knockout
Neuropeptides
Neuropilin-1
Protein Transport
Semaphorins
Signal Transduction
Vascular Endothelial Growth Factor A
