Differential functional relevance of a plasma membrane ganglioside sialidase in cholinergic and adrenergic neuroblastoma cell lines

Gangliosides located in the outer leaflet of the plasma membrane are import ant modulators of cellular functions. Our previous work has shown that in c ultured human SK-N-MC neuroblastoma cells a sialidase residing in the same membrane selectively desialylates gangliosides with terminal sialic acid re sidues, causing a shift from higher species to GM1 and a conversion of GM3 to lactosylceramide. Inhibition of this sialidase by 2-deoxy-2,3-dehydro-N- acetylneuraminic acid (NeuAc2en) resulted in increased cell proliferation a nd a loss of differentiation markers. In this study, we examined the occurr ence and function of this ganglioside sialidase in other neuronal cells. Su bcellular fractionation showed the sialidase to be located in the plasma me mbrane of all cell lines studied. The presence of the inhibitor NeuAc2en le d to a profound decrease in the amount of the differentiation marker 200 kD a/70 kDa neurofilaments and an increase in cell proliferation in the cholin ergic SK-N-MC and mixed cholinergic/adrenergic SK-N-FI and SK-N-DZ neurobla stoma lines, but had little or no effect in the human adrenergic SK-N-SH an d SK-N-AS and the adrenergic/cholinergic PC12 cells from rat. The influence of the inhibitor on cell behaviour was paralleled by a diminished number o f cholera toxin B-binding GM1 sites. The findings demonstrate that the plas ma membrane ganglioside sialidase is an important element of proliferation and differentiation control in some, but not all, neuroblastoma cells and s uggest that there might be a relationship between plasma membrane sialidase activity and cholinergic differentiation.