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J Biol Chem, Vol. 275, Issue 12, 8404-8408, March 24, 2000

A Xestospongin C-sensitive Ca²⁺ Store Is Required for cAMP-induced Ca²⁺ Influx and cAMP Oscillations in Dictyostelium^*

Ralph Schaloske, Christina Schlatterer, and Dieter Malchow

From the Faculty of Biology, University of Konstanz, Postfach 55 60, 78457 Konstanz, Germany

Xestospongin C (XeC) is known to bind to the inositol 1,4,5-trisphosphate (IP₃)-sensitive store in mammalian cells and to inhibit IP₃- and thapsigargin-induced Ca²⁺ release. In this study we show that this is also true for Dictyostelium. In addition, XeC inhibited Ca²⁺ uptake into purified vesicle fractions and induced Ca²⁺ release. This suggests that, in the case of Dictyostelium, XeC opens rather than plugs the IP₃ receptor channel as was proposed for mammalian cells (Gafni, J., Munsch, J. A., Lam, T. H., Catlin, M. C., Costa, L. G., Molinski, T. F., and Pessah, I. N. (1997) Neuron 19, 723-733). In order to elucidate the function of the XeC-sensitive Ca²⁺ store in Dictyostelium during differentiation, we applied XeC to the cells and found that it caused a time-dependent increase of basal [Ca²⁺]_i and inhibited cAMP-induced Ca²⁺ influx in single cells as well as in cell suspensions. Moreover, XeC blocked light scattering spikes and pulsatile cAMP signaling.

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