TAURINE-INDUCED NEURONAL DIFFERENTIATION - THE INFLUENCE OF CALCIUM AND THE GANGLIOSIDE GM1

Taurine-induced differentiation was examined in the murine neuroblastoma Neuro-2a cell line in the presence or absence of the monosialoganglioside GM1 and under conditions in which Ca2+ levels were manipulated. Taurine (4 mM), GM1 (200 μg/ml), or taurine with GM1 were applied to culture media that contained either various concentrations of Ca2+ or the Ca2+ ionophore A23187. Taurine or GM1 and taurine with GM1 increased the number of cells emitting neuntes above that found for controls. A significant interaction was found between treatment (taurine, GM1 or taurine+GM1) and the manipulations of Ca2+ levels, affecting the number of neuntes and producing changes on the neuritic and perikaryal surfaces. Treatment with both taurine and taurine+GM1 and the various concentrations of Ca2+ resulted in a significant increase in neurite elongation. The Ca2+ ionophore A23187 in the presence of taurine or taurine+GM1 caused neuntes to grow longer than observed in media containing Ca2+, either in a low concentration (about 125 μM) or at 1-2 mM. Taurine-treated cultures in the presence of extracellular Ca2+ or A23187 were characterized by surfaces with numerous microvillar, spine-like projections. This effect was enhanced with GM1 and was less pronounced in the medium containing low levels of Ca2+. Transmission electron microscopy of the taurine-stimulated neurons revealed an excessive number of clear-core vesicles (40-200 nm in diameter) in perikarya, neuntes and neuritic varicosities and growth cones. In addition, numerous aggregates of intermediate filaments were seen. They were most abundant in the taurine+GM1 treated cultures. The taurine+A23187 cultures also exhibited numerous microtubules within the elongated processes. The different neuritic patterns induced by taurine under conditions in which Ca2+ levels were manipulated and/or when cells were exposed to exogenous GM1 suggest that taurine's actions depend in part on Ca2+ flux. © 1990.