Neuropilin-1 regulates platelet-derived growth factor receptor signaling in mesenchymal stem cells

Stephen G Ball , Christopher Bayley , C Adrian Shuttleworth , Cay M Kielty (1)

1 Faculty of Life Sciences [Manchester]

Using human mesenchymal stem cells lacking vascular endothelial growth factor (VEGF) receptors, we show that the pro-angiogenic receptor neuropilin-1 associates with phosphorylated platelet-derived growth factor (PDGF) receptors, thereby regulating cell signaling, migration, proliferation and network assembly. Neuropilin-1 co-immunoprecipitated and co-localized with phosphorylated PDGF receptors in the presence of growth factors. Neuropilin-1 knockdown blocked PDGF-AA-induced PDGF receptor-alpha phosphorylation and migration, reduced PDGF-BB induced PDGF receptor-beta activation and migration, blocked VEGF-A activation of both PDGF receptors, and attenuated proliferation. Neuropilin-1 prominently co-localized with both PDGF receptors within mesenchymal stem cell networks assembled in matrigel and in the chorioallantoic membrane vasculature microenvironment, and its knockdown grossly disrupted network assembly and decreased PDGF receptor signaling. Thus, neuropilin-1 regulates mesenchymal stem cells by forming ligand-specific receptor complexes that direct PDGF receptor signaling, especially the PDGF receptor-alpha homodimer. This receptor crosstalk may control the mobilization of mesenchymal stem cells in neovascularization and tissue remodeling.

Mots clés: Life Sciences

Stephen G Ball, Christopher Bayley, C Adrian Shuttleworth, Cay M Kielty. Neuropilin-1 regulates platelet-derived growth factor receptor signaling in mesenchymal stem cells. Biochemical Journal, 2010, 427 (1), pp.29-40. ⟨10.1042/BJ20091512⟩. ⟨hal-00479264⟩