A neuronal cell surface heparan sulfate proteoglycan is required for dorsal root ganglion neuron stimulation of Schwann cell proliferation

Axons of dorsal root ganglion neurons express on their surfaces one or more proteins which are mitogenic for Schwann cells (Salzer, J., R. P. Bunge, and L. Glaser, 1980, J. Cell Biol., 84:767-778). Incubation of co-cultures of dorsal root ganglion neurons and Schwann cells with 4- methylumbelliferyl-beta-D-xyloside, an inhibitor of proteoglycan biosynthesis, decreases the mitogenic response of the Schwann cell by over 95%. The effect of the beta-D-xyloside has been localized to the neurons; pretreatment of neurons but not of Schwann cells with the inhibitor causes a marked reduction of the mitogenic response. In addition, Schwann cells treated with beta-D-xyloside are still mitogenically responsive to soluble Schwann cell mitogens (cholera toxin and glial growth factor). Neurons treated with heparitinase and membrane vesicles prepared from heparitinase-treated neurons show diminished mitogenicity for Schwann cells, while other proteoglycan lyases have no effect. We conclude that a cell surface heparan sulfate proteoglycan is a component of the Schwann cell mitogen present on the surface of dorsal root ganglion neurons.