DIFFERENTIAL AND CELL DEVELOPMENT-DEPENDENT LOCALIZATION OF MYELIN MESSENGER-RNAS IN OLIGODENDROCYTES

In oligodendrocytes (OLG), the mRNAs for the various myelin proteins l ocalize to different intracellular sites, Whereas the confinement of m yelin basic protein (MBP) mRNA to the processes of the cell has been w ell established, we demonstrate that most other myelin mRNA species ar e mainly present in the perinuclear region, Using in situ hybridizatio n of cultured rat OLG we found that mRNAs are localized to at least th ree different locations: 1) to the perinuclear region [myelin-associat ed glycoprotein (MAG) mRNA]; 2) mainly to the processes (the mRNA for the 14-kDa isoform of MBP); and 3) to both the perinuclear region and the primary processes [2',3'-cyclic nucleotide phosphodiesterase (CNPa se) and proteolipid protein (PLP) mRNAs], Thus, depending on their pri mary structure, the mRNA species in OLG either remain near the nucleus or localize to primary or secondary processes before their translatio n, The myelin mRNA localization correlates well with that of the prote ins encoded in them, as demonstrated by immunocytochemistry, Since dif ferent isoforms of MBP have different locations in transfected HeLa ce lls (Staugaitis et al.: J Cell Biol 110:1719-1727, 1990), we also have investigated the localization of the various mRNAs in OLG, using exon 2-minus and exon 2-specific probes for in situ hybridization, The exo n 2-minus MBP mRNAs are transported far into the processes whereas exo n 2-specific mRNA was only detected in the cell body, This suggests th at sorting and trafficking of MBP mRNA are regulated by the presence o r absence of the exon 2 sequence, Furthermore, during maturation of OL G, exon 2-plus mRNAs disappear, whereas exon 2-minus mRNAs increase, T he developmentally regulated expression of exon 2-plus transcripts sug gests a role of their protein products in differentiation rather than in myelination. (C) 1997 Wiley-Liss, Inc.