The 14-3-3 protein is an essential component of cyclic AMP signaling for regulation of chemotaxis and development in Dictyostelium.

The evolutionarily-conserved 14-3-3 proteins regulate many cellular processes through binding to various phosphorylated targets in eukaryotes. It first appears in Dictyostelium, however its role in this organism is poorly understood. Here we show that down-regulation of the 14-3-3 impairs chemotaxis and causes multiple-tip formation in Dictyostelium. Mechanistically, the 14-3-3 is a critical component of cyclic AMP (cAMP) signaling and binds to nearly a hundred of proteins in Dictyostelium, including a number of evolutionarily-conserved proteins. 14-3-3 - interaction with its targets is up-regulated in response to developmental cues/regulators including starvation, osmotic stress and cAMP. cAMP stimulates 14-3-3 - binding to phospho-Ser431 on a guanine nucleotide exchange factor Gef-Q. Interestingly, overexpression of Gef-Q(Ser431Ala) mutant but not wild-type Gef-Q protein causes a multiple-tip phenotype in Dictyostelium, which partially resembles phenotypes of the 14-33 - deficient mutant. Collectively, these data demonstrate that the 14-3-3 plays an important role in Dictyostelium and may help to deepen our understanding of the evolution of 14-3-3 - interactomes in eukaryotes.