Developmental changes of tau protein and mRNA in cultured rat brain oligodendrocytes

Oligodendrocytes elaborate an extensive network of multibranched processes and flat membranous sheets. Microtubules (MT) participate in the elaboratio n and stabilization of myelin-forming processes and are essential for cellu lar sorting processes. Microtubule-associated proteins (MAPS) are involved in the regulation and stabilization of the dynamic MT network. It has been shown previously that oligodendrocytes express the MAP tau, a phosphoprotei n most abundant in neurons of the CNS. In this article, we demonstrate for the first time that oligodendrocytes contain all six tau isoforms, and that tau mRNA and protein expression is developmentally regulated. Immunoblot a nalysis reveals that tau protein is more abundant, and mature isoforms are more prominent at later stages of development. During the first week of cul ture maturation, a marked decrease in phosphorylation is observable. Using an RT-PCR approach, we can show that oligodendrocytes express small amounts of exon 3 containing isoforms and that during culture maturation, tau mRNA splice products with 3 MT-binding domains (3R) decrease and mRNA with 4 MT -binding domains (4R) increase. In situ hybridization study demonstrates th at tau mRNA is present in precursor cells and in mature oligodendrocytes. T au mRNA is actively transported into the cellular processes, is specificall y present in the primary and some of the secondary processes, enriched at t he turning and branching points and the growing tips, and often appears as small patches. Hence, localized tau translation at specific sites in the ce llular extensions might contribute to the regulation of MT stability during process formation, early axonal contact establishment, and myelination. (C ) 2001 Wiley-Liss, Inc.