Myelin basic protein mediates extracellular signals that regulate microtubule stability in oligodendrocyte membrane sheets
Article first published online: 11 OCT 2004
Copyright © 1994 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 39, Issue 1, pages 97–107, 1 September 1994
How to Cite
Dyer, C. A., Philibotte, T. M., Wolf, M. K. and Billings-Gagliardi, S. (1994), Myelin basic protein mediates extracellular signals that regulate microtubule stability in oligodendrocyte membrane sheets. J. Neurosci. Res., 39: 97–107. doi: 10.1002/jnr.490390112
- Issue published online: 11 OCT 2004
- Article first published online: 11 OCT 2004
- Manuscript Accepted: 10 JUN 1994
- Manuscript Revised: 9 JUN 1994
- Manuscript Received: 6 MAY 1994
- This work was carried out in the Jeffery M. Pratt labo-ratory and was supported by the National Multiple Scle-rosis Society grantRG2514-A-1, NIH NS-I 1425, NIH NS-13143 and bythe Department of Mental Retardation of the Commonwealth of Massachusetts(contract 100220023SC).
- myelin/oligodendrocyte specific protein;
Treatment of cultured oligodendrocytes with a monoclonal antibody to galactocerebroside (GalC) triggers a cascade of events including the redistribution 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 (MBP)-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 cultured oligodendrocytes. We now show that MBP and GalC, which are both initially Triton X-100 soluble, become Triton X-100 insoluble following anti-GalC binding and anti-GalC:GalC complex redistribution, suggesting that the surface anti-GalC: GalC complexes become associated with cytoplasmic MBP. Mediation of the signaling event by MBP is further demonstrated by (1) a decreased phosphorylation of MBP in wild type oligodendrocytes after antibody binding, and (2) the absence of responses, such as GalC redistribution and microtubule loss, in MBP-deficient shiverer 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 morphology that is similar to MBP-deficient shiverer oligodendrocytes. A second signaling pathway which produces an opposite effect, i.e., the stabilization and apparent up-regulation of microtubular structures in cultured oligodendrocyte membrane sheets, remains functional in shiverer oligodendrocytes. Thus, MBP appears to be important for mediating extracellular signals that cause a loss of microtubular structures in oligodendrocyte membrane sheets and abnormal morphology. Copyright © 1994 Wiley-Liss, Inc.