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 NRP1, with the requirement of the C-terminal Arg residue of PDGF-D. 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, independent of PDGFRβ, altering the availability of NRP1 for VEGF-A/VEGF receptor 2 signaling. PDGF-D showed differential effects on pericyte behavior in ex vivo sprouting assays, compared to PDGF-B. Furthermore, PDGF-D induced PDGFRβ/NRP1 interaction in the trans-configuration between endothelial cells and pericytes.
In summary, we show that NRP1 can act as a co-receptor for PDGF-D in PDGFRβ signaling, possibly implicated in intercellular communication in the vascular wall.
- Received December 7, 2016.
- Accepted February 19, 2017.
- © 2017. Published by The Company of Biologists Ltd