title: Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer.
abstract: 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.
authors.affiliation: Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Cai
authors.forename: Mariko
authors.initials: M
authors.lastname: Katoh-Kurasawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Muramoto
authors.forename: Balaji
authors.initials: B
authors.lastname: Santhanam
authors.forename: Yu
authors.initials: Y
authors.lastname: Long
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ueda
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Iglesias
authors.forename: Gad
authors.initials: G
authors.lastname: Shaulsky
authors.forename: Peter N
authors.initials: PN
authors.lastname: Devreotes
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D004023:Dictyostelium / Q000254:growth & development / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D019913:Nuclear Localization Signals; D010766:Phosphorylation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D050980:GATA Transcription Factors; D019913:Nuclear Localization Signals; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins