SPALTEN, A PROTEIN CONTAINING G-ALPHA-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 D ictyostelium multicellular development. Spn encodes a protein with an amino-terminal domain that shows very high homology to G alpha-protein subunits, a highly charged inter-region, and a carboxy-terminal domai n that encodes a functional PP2C. Spn is essential for development pas t the mound stage, being required cell autonomously for prestalk gene expression and nonautonomously for prespore cell differentiation. Muta tional analysis demonstrates that the PP2C domain is the Spn effector domain and is essential for Spn function, whereas the G alpha-like dom ain is required for membrane targeting and regulation of Spn function. Moreover, Spn carrying mutations in the G alpha-like domain that do n ot affect membrane targeting but affect specificity of guanine nucleot ide binding in known GTP-binding proteins are unable to fully compleme nt the spn(-) phenotype, suggesting that the G alpha-like domain regul ates Spn function either directly or indirectly by mediating its inter actions with other proteins. Our results suggest that Spn encodes a si gnaling molecule with a novel G alpha-like regulatory domain.