PDGF-D is a ligand for NRP1

The platelet-derived growth factor (PDGF) family of growth factors comprises four different genes that form five dimeric isoforms. PDGF-D, the most recently discovered member of the family, is a ligand for PDGF receptor β (PDGFRβ), and has an essential role in the regulation of a number of different processes, including cell proliferation, migration, survival and chemotaxis. Its biology, however, has remained largely unexplored. Now (p. 1365), Lars Muhl, Ulf Eriksson and colleagues show that PDGF-D binds to the multifunctional transmembrane receptor protein neuropilin 1 (NRP1), and they delineate the structural basis underlying this interaction. The authors demonstrate that the PDGF-D induces the interaction of PDGFRβ and NRP1, and this interaction is dependent on the PDGF-D C-terminal Arg370 residue. Moreover, the NRP1–PDGFRβ complexes can occur in trans between pericytes and endothelial cells. Furthermore, the authors show that PDGF-D stimulation induces NRP1 translocation to endothelial cell–cell junctions independently of PDGFRβ, possibly altering the availability of NRP1 for VEGF-A and VEGF receptor 2 signalling. These data show that PDGF-D is a ligand for NRP1, a previously unrecognised feature of PDGF-D.