GLYCOLIPID SIALYLTRANSFERASES ARE ENHANCED DURING NEURAL DIFFERENTIATION OF MOUSE EMBRYONIC CARCINOMA-CELLS, P19

We have studied ganglioside alterations and their enzymatic basis duri ng the course of neural differentiation of mouse embryonic carcinoma c ell line P19. This cell line can differentiate into neurons and astroc ytes on cell aggregation after treatment with retinoic acid (RA) or in to muscle cells on dimethyl sulfoxide (DMSO) treatment. GD3, detected on immunostaining after thin-layer chromatography (TLC) with monoclona l antibody (MAb) R24, was markedly present in aggregates treated with RA. GM3 synthase (alpha 2,3-sialyltransferase, SAT-I) in neurons was f ound to exhibit the highest activity. GD3 synthase (alpha 2,8-sialyltr ansferase, SAT-II) and GD3 synthase mRNA, as analyzed by Northern blot ting, were also markedly present in aggregates and neurons induced by Rk However, on treatment with DMSO, which induces muscle cells, there was no change in the level of GD3 synthase activity, and its transcrip t was hardly detected during the course of muscle differentiation. GT1 b synthase (alpha 2,3-sialyltransferase, SAT-IV) was present at simila r levels in undifferentiated cells and aggregates treated with RA,but a higher level was observed in neurons. On the other hand, the level o f GQ1b synthase (alpha 2,8-sialyltransferase, SAT-V) in RA-induced agg regates was significantly higher than that in neurons. These results s how that RA but not DMSO induces the expression of GM3, GD3, GT1b and GQ1b synthases, and particularly GD3 synthase mRNA, in the ganglioside biosynthetic pathway during the neural differentiation of embryonic c arcinoma P19 cells. (C) 1997 Academic Press.