A novel microtubule-associated protein-2 expressed in oligodendrocytes in multiple sclerosis lesions.
Elucidation of the mechanisms involved in the regeneration of oligodendrocytes and remyelination is a central issue in multiple sclerosis (MS) research. We recently identified a novel alternatively spliced, developmentally regulated oligodendrocyte-specific protein designated microtubule-associated protein-2+13 [microtubule-associated protein-2 expressing exon 13 (MAP-2+13)]. MAP-2+13 is expressed in human fetal oligodendrocytes during process extension and myelination but is minimally expressed in normal mature CNS. To test the hypothesis that MAP-2+13 is reexpressed in regenerating oligodendrocytes in MS lesions, we examined the brains of MS patients for the expression of this protein. By immunocytochemistry using a series of monoclonal antibodies specific for MAP-2+13, we determined that MAP-2+13 expression was up-regulated in all 31 lesions from 10 different MS brains. MAP-2+13 was expressed in regenerating oligodendrocytes associated with demyelinated lesions, with the highest counts found in regions of extensive remyelination. By electron microscopy, MAP-2+13 was localized to oligodendrocytes engaged in remyelination, evident by their process extension and association with thinly myelinated (remyelinated) and demyelinated axons. These results suggest a hitherto unsuspected role for this microtubule-associated protein in oligodendrocyte function during development and myelin repair.
Shafit-Zagardo
B
B
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Kress
Y
Y
Zhao
M L
ML
Lee
S C
SC
D000328:Adult; D000368:Aged; D001369:Axons / Q000473:pathology; D005091:Exons / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification*; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009186:Myelin Sheath / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D020336:Paraparesis, Spastic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins