Cell Biology

Slime Mold on Steroids

Science Signaling  17 Feb 2009:
Vol. 2, Issue 58, pp. ec63
DOI: 10.1126/scisignal.258ec63

The final step in fruiting body formation in the slime mold Dictyostelium discoideum is encapsulation of the spore-forming cells, a process that is tightly regulated by signaling molecules secreted by both prestalk and prespore cells to prevent the spores from becoming nonmotile before they reach their final position at the top of the stalk. Sporulation is promoted by γ-aminobutyric acid (GABA) binding to the G protein–coupled receptor (GPCR) GrlE and opposed by glutamate, which also binds to GrlE. Anjard et al. report that, whereas the glutamate signal was transduced through a heterotrimeric G protein that included Gα9, GABA signaling required Gα7. Analysis of sporulation in various Gα mutants revealed that Gα4 was required for sporulation downstream of the GPCR GrlA but did not mediate signaling from any of the known sporulation regulators. The authors isolated a hydrophobic, chloroform-soluble factor that induced sporulation by signaling through GrlA and Gα4, which they named spore differentiation factor 3 (SDF-3). SDF-3 induced sporulation less rapidly than did SDF-2, a peptide produced in response to GABA signaling through GrlE and Gα7, and SDF-3–induced sporulation required GrlA, Gα4, GABA, and GrlE, suggesting that it acted upstream of GABA. Several steroids, of which hydrocortisone was the most potent, mimicked the sporulation-inducing effects of SDF-3, including GABA release and SDF-2 accumulation. Steroid biosynthesis inhibitors prevented precocious sporulation in rapid-sporulation mutants, and this effect could be overcome by the application of purified SDF-3. Although the precise chemical identity of this steroid has not yet been determined, it is thus far the earliest identified signal that triggers terminal differentiation of Dictyostelium spores.

C. Anjard, Y. Su, W. F. Loomis, Steroids initiate a signaling cascade that triggers rapid sporulation in Dictyostelium. Development 136, 803–812 (2009). [Abstract] [Full Text]