The pathobiology of myelin mutants reveal novel biological functions of the MBP and PLP genes

Substantial biological data indicate that the myelin basic protein (MBP) an d myelin proteolipid protein (PLP/DM20) genes produce products with functio ns beyond that of serving as myelin structural proteins. Much of this evide nce comes from studies on naturally-occurring and man-made mutations of the se genes in mice and other species. This review focuses upon recent evidenc e showing the existence of other products of these genes that may account f or some of these other functions, and recent studies providing evidence for alternative biological functions of PLP/DM20. The MBP and PLP/DM20 genes e ach encode the classic MBP and PLP isoforms, as well as a second family of proteins that are not involved in myelin structure. The biological roles of these other products of the genes are becoming clarified. The non-classic MBP gene products appear to be components of transcriptional complexes in t he nucleus, and they also may be involved in signaling pathways in T-cells and in neural cells. The non-classic PLP/DM20 gene products appear to be co mponents of intracellular transport vesicles in oligodendrocytes. There is evidence for other functions of the classic PLP/DM20 proteins, including a role in neural cell death mechanisms, autocrine and paracrine regulation of oligodendrocytes and neurons, intracellular transport and oligodendrocyte migration.