The proliferation of Schwann cells is, in part, controlled by interaction with appropriate axons, both in vivo and in vitro. Schwann cells in pure populations in tissue culture remain quiescent unless in contact with axons or membrane fragments derived from axons. We have recently found that the mitogenic response of Schwann cells to the neurites of cultured neurons also occurs when these cells come in contact with PC-12 cells, an established rat pheochromocytoma cell line. This observation provides, for the first time, access to an adequate supply of the neurite mitogen for purification and characterization. We propose to purify the specific protein(s) present on the surface of PC-12 rat phechromocytoma cells which is mitogenic for Schwann cells. Initial observations indicate that the PC-12 mitogen is analogous in function to the mitogen present on the surface of dorsal root ganglia neurites. These mitogens are different from previously identified polypeptide hormones (mitogens), and are presumed to serve to regulate the growth of Schwann cells during normal development. The purified proteins will be characterized and the interaction of these specific growth factors with receptors on the surface of Schwann cells will be studied. The role of 3', 5' cyclic adenosine monophosphate, protein phosphorylation and ion fluxes in the mitogenic response of Schwann cells to these neurite mitogens and to other growth factors, known from previous work to influence Schwann cell proliferation, will be investigated.
