Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Science. 2014 Mar 21;343(6177):1249531. doi: 10.1126/science.1249531.
Biological oscillations are observed at many levels of cellular organization. In the social amoeba Dictyostelium discoideum, starvation-triggered multicellular development is organized by periodic cyclic adenosine 3',5'-monophosphate (cAMP) waves, which provide both chemoattractant gradients and developmental signals. We report that GtaC, a GATA transcription factor, exhibits rapid nucleocytoplasmic shuttling in response to cAMP waves. This behavior requires coordinated action of a nuclear localization signal and reversible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor-mediated phosphorylation. Although both are required for developmental gene expression, receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle. We demonstrate that this biological circuit filters out high-frequency signals and counts those admitted, thereby enabling cells to modulate gene expression according to the dynamic pattern of the external stimuli.
生物振荡在细胞组织的多个层次上都有观察到。在社会性粘菌 Dictyostelium discoideum 中,饥饿触发的多细胞发育是由周期性的环腺苷酸 3',5'-单磷酸(cAMP)波组织的,这些波提供了趋化梯度和发育信号。我们报告说,GtaC,一种 GATA 转录因子,在响应 cAMP 波时表现出快速的核质穿梭。这种行为需要核定位信号和可逆 G 蛋白(异三聚体鸟苷酸结合蛋白)偶联受体介导的磷酸化的协调作用。虽然这两者对于发育基因表达都是必需的,但受体占据促进 GtaC 的核输出,从而导致在每个 cAMP 循环中短暂的转录爆发。我们证明,这种生物电路可以滤除高频信号并计数那些被允许通过的信号,从而使细胞能够根据外部刺激的动态模式来调节基因表达。