Nucleocytoplasmic Shuttling of a GATA Transcription Factor Functions as a Development Timer

• Published in: Science (American Association for the Advancement of Science) Vol. 343; no. 6177; p. 1329
• Main Authors: Cai, Huaqing, Katoh-Kurasawa, Mariko, Muramoto, Tetsuya, Santhanam, Balaji, Long, Yu, Li, Lei, Ueda, Masahiro, Iglesias, Pablo A., Shaulsky, Gad, Devreotes, Peter N.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 21.03.2014; The American Association for the Advancement of Science
• Subjects: Active Transport, Cell Nucleus; Cell Nucleus - metabolism; Computer Simulation; Cyclic AMP - metabolism; Cyclic AMP - pharmacology; Cytoplasm - metabolism; Dictyostelium - growth & development; Dictyostelium - metabolism; GATA Transcription Factors - chemistry; GATA Transcription Factors - genetics; GATA Transcription Factors - metabolism; Gene Expression Regulation; Heterotrimeric GTP-Binding Proteins - metabolism; Individualized Instruction; Nuclear Localization Signals; Phosphorylation; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Receptors, G-Protein-Coupled - metabolism; RESEARCH ARTICLE SUMMARY; Stimuli
• ISSN: 0036-8075; 1095-9203
• 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.