Temperature-sensitive Gβ mutants discriminate between G protein-dependent and -independent signaling mediated by serpentine receptors

Deletion of the single gene for the Dictyostelium G protein β-subunit blocks development at an early stage. We have now isolated temperature-sensitive alleles of Gβ to investigate its role in later development. We show that Gβ is directly required for adenylyl cyclase A activation and for morphogenetic signaling during the entire developmental program. Gβ was also essential for induction of aggregative gene expression by cAMP pulses, a process that is mediated by serpentine cAMP receptors (cARs). However, Gβ was not required for cAR-mediated induction of prespore genes and repression of stalk genes, and neither was Gβ needed for induction of prestalk genes by the differentiation inducing factor (DIF). cAMP induction of prespore genes and repression of stalk genes is mediated by the protein kinase GSK-3. GSK-3 also determines cell-type specification in insects and vertebrates and is regulated by the wingless/wnt morphogens that are detected by serpentine fz receptors. The G protein-dependent and -independent modes of cAR-mediated signaling reported here may also exist for the wingless/wnt signaling pathways in higher organisms.