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 14-3-3 − 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.

进化上保守的 14-3-3 蛋白通过与真核生物中的各种磷酸化靶标结合来调节许多细胞过程。它首先出现在网基网柄菌中，但是它在这个生物体中的作用却知之甚少。在这里，我们表明 14-3-3 的下调会损害趋化性并导致网基网柄菌中的多尖端形成。从机制上讲，14-3-3 是环 AMP (cAMP) 信号传导的关键组成部分，并与网基网柄菌中的近百种蛋白质结合，包括许多进化上保守的蛋白质。14-3-3 - 与其靶标的相互作用被上调以响应发育线索/调节剂，包括饥饿、渗透压力和cAMP。cAMP 刺激 14-3-3 - 与鸟嘌呤核苷酸交换因子 Gef-Q 上的磷酸化 Ser431 结合。有趣的是，Gef-Q ^Ser431Ala突变体而非野生型 Gef-Q 蛋白的过度表达导致网基网柄菌中的多尖端表型，这部分类似于 14-3-3 - 缺陷突变体的表型。总的来说，这些数据表明 14-3-3 在网基网柄菌中起着重要作用，可能有助于加深我们对真核生物中 14-3-3 - 相互作用组进化的理解。