Ganglioside-induced terminal differentiation of human keratinocytes: early biochemical events in signal transduction

Previous studies have indicated that GQ_1b, a tetrasialoganglioside containing two disialosyl residues, may be an important regulator of cellular differentiation in murine keratinocytes. In the present study, we examined the effect of gangliosides on the differentiation of human keratinocytes. Current evidence indicates that GQ_1b induces cornified envelope formation and enhancement of transglutaminase (TGase) activity, which are characteristic parameters of terminal differentiation in human cultured keratinocytes, while the other gangliosides, GT_1b and GM₁, are much less effective. The mass contents of inositol 1,4,5-trisphosphate (1,4,5-IP₃) and the intracellular calcium concentration ([Ca⁺]_i) were also measured in keratinocytes exposed to gangliosides. A rapid increase in 1,4,5-IP₃ occurred at 30 s following stimulation, but no significant difference at the maximum level was observed among the three gangliosides in contrast to the finding in murine keratinocytes. In addition, [Ca⁺] increases occurred concurrently with the 1,4,5-IP₃ generation by the three gangliosides. On the other hand, [Ca⁺] transients were unaffected by chelating extracellular Ca⁺ with EGTA. It is thus considered that the mobilization by 1,4,5-IP₃ from internal stores plays a crucial role. These [Ca⁺]_i profiles were also indistinguishable between the gangliosides. Taken together, in human keratinocytes, gangliosides differentially affect some other as yet unidentified site(s) in the post-calcium transmission pathway(s) which leads to TGase activation.