MYELIN BASIC-PROTEIN MEDIATES EXTRACELLULAR SIGNALS THAT REGULATE MICROTUBULE STABILITY IN OLIGODENDROCYTE MEMBRANE SHEETS

Treatment of cultured oligodendrocytes with a monoclonal antibody to g alactocerebroside (GalC) triggers a cascade of events including the re distribution of membrane surface GalC over internal domains of MBP and loss of microtubular structures within the sheets (Dyer and Benjamins : J Neurosci 8:4307-4318, 1988; Dyer and Benjamins: J Neurosci Res 24: 212-221, 1989). In this report, wild type and myelin basic protein (MB P)-deficient shiverer oligodendrocytes were used to study the possible relationships between these events, and specifically to determine if MBP mediates signals which destabilize microtubular assemblies in cult ured oligodendrocytes. We now show that MBP and GalC, which are both i nitially Triton X-100 soluble, become Triton X-100 insoluble following anti-GalC binding and anti-GalC:GalC complex redistribution, suggesti ng that the surface anti-GalC: GalC complexes become associated with c ytoplasmic MBP. Mediation of the signaling event by MBP is further dem onstrated by 1) a decreased phosphorylation of MBP in wild type oligod endrocytes after antibody binding, and 2) the absence of responses, su ch as GalC redistribution and microtubule loss, in MBP-deficient shive rer oligodendrocytes treated with anti-GalC. Continuous activation of the GalC/MBP pathway for 7 days in wild type oligodendrocytes results in enlarged cell bodies and production of numerous microprocesses, a m orphology that is similar to MBP-deficient shiverer oligodendrocytes. A second signaling pathway which produces an opposite effect, i.e., th e stabilization and apparent up-regulation of microtubular structures in cultured oligodendrocyte membrane sheets, remains functional in shi verer oligodendrocytes. Thus, MBP appears to be important for mediatin g extracellular signals that cause a loss of microtubular structures i n oligodendrocyte brane sheets and abnormal morphology. (C) 1994 Wiley -Liss, Inc.