Spalten, a protein containing Gα-protein-like and PP2C domains, is essential for cell-type differentiation in Dictyostelium

We have identified a novel gene, Spalten (Spn) that is essential for Dictyostelium multicellular development. Spn encodes a protein with an amino-terminal domain that shows very high homology to Gα-protein subunits, a highly charged inter-region, and a carboxy-terminal domain that encodes a functional PP2C. Spn is essential for development past the mound stage, being required cell autonomously for prestalk gene expression and nonautonomously for prespore cell differentiation. Mutational analysis demonstrates that the PP2C domain is the Spn effector domain and is essential for Spn function, whereas the Gα-like domain is required for membrane targeting and regulation of Spn function. Moreover, Spn carrying mutations in the Gα-like domain that do not affect membrane targeting but affect specificity of guanine nucleotide binding in known GTP-binding proteins are unable to fully complement the spn−phenotype, suggesting that the Gα-like domain regulates Spn function either directly or indirectly by mediating its interactions with other proteins. Our results suggest that Spn encodes a signaling molecule with a novel Gα-like regulatory domain.