PT  - JOURNAL ARTICLE
AU  - C. B. Marta
AU  - C. M. Taylor
AU  - T. Coetzee
AU  - T. Kim
AU  - S. Winkler
AU  - R. Bansal
AU  - S. E. Pfeiffer
TI  - Antibody Cross-Linking of Myelin Oligodendrocyte Glycoprotein Leads to Its Rapid Repartitioning into Detergent-Insoluble Fractions, and Altered Protein Phosphorylation and Cell Morphology
AID  - 10.1523/JNEUROSCI.23-13-05461.2003
DP  - 2003 Jul 02
TA  - The Journal of Neuroscience
PG  - 5461--5471
VI  - 23
IP  - 13
4099  - http://www.jneurosci.org/content/23/13/5461.short
4100  - http://www.jneurosci.org/content/23/13/5461.full
SO  - J. Neurosci.2003 Jul 02; 23
AB  - Myelin oligodendrocyte glycoprotein (MOG) is, quantitatively, a relatively minor component of the myelin membrane. Nevertheless, peritoneal administration of MOG evokes potent cellular and humoral immunoreactivity, resulting in an experimental allergic encephalitis with immunopathology similar to multiple sclerosis. Moreover, antibodies against MOG cause myelin destruction in situ. Therefore, it appears that MOG-related demyelination is dependent on anti-MOG antibody, but the mechanism(s) by which it occurs is unclear. Of potential significance are observations that some proteins are selectively partitioned into specialized plasma membrane microdomains rich in glycosphingolipids and cholesterol (“lipid rafts”). In particular, during ligand or antibody cross-linking, various plasma membrane receptors undergo enhanced partitioning into rafts as an obligatory first step toward participation in early signal transduction events. In contrast to mature myelin, in oligodendrocytes (OLs) in culture MOG is not raft associated [Triton X-100 (TX-100) soluble, 4°C]. However, in this study we show that antibody cross-linking (anti-MOG plus secondary antibody) of MOG on the surface of OLs results in the repartitioning of ∼95% of MOG into the TX-100-insoluble fraction. This repartitioning of MOG is rapid (≤1 min), antibody dose dependent, requires an intact cytoskeleton, leads to phosphorylation or dephosphorylation of tyrosine, serine, and threonine residues in specific proteins (e.g., β-tubulin, Gβ1–2), and invokes a rapid retraction of OL processes. After removal of the cross-linking antibodies, these events are reversed. We hypothesize that antibody-mediated repartitioning of MOG into TX-100-insoluble glycosphingolipid–cholesterol-rich microdomains initiates specific cellular signaling that could be related to initial steps of MOG-mediated demyelination.