title: Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling.
abstract: Platelet-derived growth factor (PDGF)-D is a PDGF receptor β (PDGFRβ)-specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood. In this study, we demonstrate that PDGF-D binds directly to neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. Stimulation with PDGF-D, but not PDGF-B, induced PDGFRβ-NRP1 complex formation in fibroblasts. Additionally, PDGF-D induced translocation of NRP1 to cell-cell junctions in endothelial cells, independently of PDGFRβ, altering the availability of NRP1 for VEGF-A-VEGFR2 signaling. PDGF-D showed differential effects on pericyte behavior inex vivosprouting assays compared to PDGF-B. Furthermore, PDGF-D-induced PDGFRβ-NRP1 interaction can occur intransbetween molecules located in different cells (endothelial cells and pericytes). In summary, we show that NRP1 can act as a co-receptor for PDGF-D-PDGFRβ signaling and is possibly implicated in intercellular communication in the vascular wall.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden lars.muhl@ki.se.
authors.forename: Lars
authors.identifier: 0000-0003-0952-0507
authors.initials: L
authors.lastname: Muhl
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Erika Bergsten
authors.initials: EB
authors.lastname: Folestad
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Gladh
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Moessinger
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Jakobsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles väg 2, A3:P4, Stockholm S-17177, Sweden.
authors.forename: Ulf
authors.identifier: 0000-0002-4439-3980
authors.initials: U
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D039942:Neuropilin-1 / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013552:Swine
chemical_list: D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D039942:Neuropilin-1; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Co-receptor; Endothelial cells; NRP1; PDGF-D; Pericyte; Trans-signaling