ST8Sia IV mRNA corresponds with the biosynthesis of alpha 2,8Sialyl polymers but not oligomers in rat oligodendrocytes

As oligodendrocytes mature they progress through a series of distinct diffe rentiation steps characterized by the expression of specific markers. One s uch marker, polysialic acid found on the neural cell adhesion molecule (NCA M), is detected by antibodies and is present on progenitor oligodendrocytes , but is not detected to the same extent on mature oligodendrocytes. Two cl osely related polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST) h ave been cloned previously and shown to synthesize polysialic acid on NCAM and other glycoproteins. To determine whether or not poly alpha2,8sialyltra nsferases are downregulated during the differentiation of oligodendrocytes, the enzyme activity and expression of ST8Sia II and ST8Sia IV mRNA at two stages of maturation in JS12/1 and JS3/16 oligodendrocytes were examined. D ifferentiation in both oligodendroglial cell lines was accompanied by more than a 50% reduction in the biosynthesis of polymers of alpha2,8siailc acid when fetuin was used as substrate. Most interestingly, extracts of JS12/1 mature cells synthesized 60% more short oligomers of alpha2,8sialic acid th an the progenitor cells, whereas JS3/16 mature cells synthesized barely det ectable amounts of the short oligomers. Transcripts for ST8Sia IV mRNA were present in both JS12/1 and JS3/16 and were reduced when the biosynthesis w as markedly reduced. In contrast ST8Sia II mRNA was barely detectable in JS 3/16 cells and although detectable in JS12/1 cells, there was no clear modu lation with maturation. These results were supported by the examination of the brains of rats from embryonic to Day 21 ages. The enzyme activity and m RNA experiments show that poly alpha2,8sialyltransferase itself is down reg ulated to cause the reduction in sialyl polymers on mature oligodendrocytes . Moreover, ST8Sia IV is responsible for the polysialylation of NCAM in oli godendrocytes. (C) 2001 Wiley-Liss, Inc.