Cytoplasmic Ca2+ and H+ concentrations determine cell fate in Dictyostelium discoideum.

A putative morphogen, called differentiation-inducing factor (DIF), is essential for stalk cell differentiation in the cellular slime mold, Dictyostelium discoideum. To investigate the relationship between the signal molecule (DIF) and the concentrations of cytoplasmic calcium ions and proton, we have examined the effects of thapsigargin (Tg) and 5,5-dimethyl-2,4-oxazolidinedione (DMO) on cell differentiation of a mutant strain HM44, which is defective in DIF production. Tg is a specific inhibitor of the Ca(2+)-ATPase present in endoplasmic and sarcoplasmic reticula, and raises the cytoplasmic calcium concentration. DMO is a reagent that decreases intracellular pH. When HM44 cells were incubated with Tg or DMO in the absence of DIF, a fraction of the cells was induced to stalk cells. If added together, these reagents induced stalk cell differentiation at high efficiency (70-80%), comparable to that attained with exogenous DIF. In the presence of the reagents, the efficiency was not much affected by lowering cell density, which suggests that the effect (stalk induction) of these reagents was not exerted through the stimulation of DIF production. Thus, these results indicate that a rise in cytoplasmic calcium and proton concentrations triggers stalk cell differentiation possibly by mimicking the roles of DIF.