Activated Gα Subunits Can Inhibit Multiple Signal Transduction Pathways during Dictyostelium Development

Abstract

Mutations impairing the GTPase activity of G protein Gα subunits can result in activated Gα subunits that affect signal transduction and cellular responses and, in some cases, promote tumor formation. An analogous mutation in the Dictyostelium Gα4 subunit gene (Q200L substitution) was constructed and found to inhibit Gα4-mediated responses to folic acid, including the accumulation of cyclic nucleotides and chemotactic cell movement. The Gα4-Q200L subunit also severely inhibited responses to cAMP, including cyclic nucleotide accumulation, cAMP chemotaxis, and cellular aggregation. An analogous mutation in the Gα2 subunit (Q208L substitution), previously reported to inhibit cAMP responses (K. Okaichi et al., 1992, Mol. Biol. Cell 3, 735–747), was also found to partially inhibit folic acid chemotaxis. Chemotactic responses to folic acid and cAMP and developmental aggregation were also inhibited by a mutant Gα5 subunit with the analogous alteration (Q199L substitution). All aggregation-defective Gα mutants were capable of multicellular development after a temporary incubation at 4°C and this development was found to be dependent on wild-type Gα4 function. This study indicates that mutant Gα subunits can inhibit signal transduction pathways mediated by other Gα subunits.