Myelin basic protein and myelin basic protein peptides induce the proliferation of Schwann cells via ganglioside GM1 and the FGF receptor

Myelin basic protein (MBP) and two peptides derived from MBP (MBP_{1- 44} and MBP_152-167) stimulated Schwann cell (SC) proliferation in a cAMP-mediated process. The two mitogenic regions of MBP did not compete with one another for binding to SC suggesting a distinctive SC receptor for each mitogenic peptide. Neutralizing antibodies to the fibroblast growth factor receptor blocked the mitogenic effect of the myelin-related SC mitogen found in the supernatant of myelin-fed macrophages. The binding of ¹²⁵I-MBP to Schwann cells was specifically inhibited by basic fibroblast growth factor (bFGF) and conversely the binding of ¹²⁵I-bFGF was competitively inhibited by MBP. These data suggested that the mitogenic effect of one MBP peptide was mediated by a bFGF receptor. The binding of MBP to ganglioside GM1 and the ability of MBP peptides containing homology to the B subunit of cholera toxin (which binds ganglioside GM1) to compete for the binding of a mitogenic peptide (MBP_1-44) to SC, identified ganglioside GM1 as a second SC receptor. Based on these results, we conclude that MBP_1-44 and MBP_152-167 associate with ganglioside GM1 and the bFGF receptor respectively to stimulate SC mitosis.