title: Developmental regulation of alternatively spliced isoforms of mRNA encoding MAP2 and tau in rat brain oligodendrocytes during culture maturation.
abstract: Oligodendrocytes are responsible for the formation and maintenance of the myelin sheaths in the central nervous system (CNS), and microtubules essentially participate in the elaboration and stabilization of myelin-containing cellular processes. We have shown before that the two major groups of neuronal microtubule-associated proteins (MAPs), MAP2 and tau, are expressed in the myelin forming cells of the CNS (Mueller et al. [1997] Cell Tissue Res. 288:239-249). Here we demonstrate for the first time that during culture maturation, changes in mRNA splicing and a shift from immature to mature MAP2 and tau mRNAs occur in oligodendrocytes. Similarly to neurons, a developmental shift from MAP2 isoforms with 3 microtubule (MT)-binding domains (3R) to the isoforms with 4 MT-binding domains (4R) is observable. MAP2c constitutes the major MAP2 isoform in oligodendrocytes. They contain tau mRNA splice products with both 3 and 4 MT-binding repeats (3R, 4R) with no amino terminal insert or with exon 2, and do not express isoforms containing exon 3. The shortest form tau 1 (3R; no inserts) representing the immature tau isoform is most prominently expressed in early progenitor cells and gradually decreases during culture maturation, while tau 5 (4R; with exon 2) appears later during in vitro differentiation. The product corresponding to tau 2 (3R; with exon 2) and tau 4 (4R; no inserts) remains approximately at the same level. Hence, the occurrence of MAPs in oligodendrocytes is developmentally regulated. While in progenitor cells, 3R- and 4R-MAP2c are expressed at approximately the same level, in mature oligodendrocytes after 12 days in vitro, the ratio of 4R- to 3R-MAP2c is nearly 2. In contrast, the ratio of 4R- to 3R-tau in progenitor cells is 1:3 and shifts to 1:1 after 12 days in culture.
authors.affiliation: Department of Biology, University of Oldenburg, Germany. CRL@Biologie.UNI-Oldenburg.DE
authors.forename: C
authors.initials: C
authors.lastname: Richter-Landsberg
authors.forename: M
authors.initials: M
authors.lastname: Gorath
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics*; D008870:Microtubules / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016875:tau Proteins