title: The calcineurin dependent transcription factor TacA is involved in development and the stress response of Dictyostelium discoideum.
abstract: Calcineurin is an important signalling protein in a plethora of Ca(2+)-regulated cellular processes. In contrast to what is known about the function of calcineurin in various organisms, information on calcineurin substrates is still limited. Here we describe the identification and characterisation of the transcription factor activated by calcineurin (TacA) in the model organism Dictyostelium discoideum. TacA is a putative zinc-finger transcription factor orthologue of yeast Crz1. In resting unstimulated cells the protein is located in the cytosol and translocates to the nucleus in a calcineurin-dependent manner after Ca(2+)-stimulation. Nuclear export of TacA is partially dependent on GskA, the Dictyostelium orthologue of mammalian GSK3. The expression of tacA is developmentally regulated with its kinetics roughly paralleling calcineurin regulation. Silencing of tacA via RNAi leads to developmental defects and dysregulation of developmentally regulated and Ca(2+)-regulated marker genes. Additionally, TacA is involved in the stress response of D. discoideum during development in a separate pathway to the well-known stress response in Dictyostelium via STATc. Finally we provide evidence that TacA is not only an orthologue of yeast Crz1 but also functionally related to mammalian NFAT.
authors.affiliation: Institute for Biology - Microbiology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany. sascha.thewes@fu-berlin.de
authors.forename: Sascha
authors.initials: S
authors.lastname: Thewes
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krohn
authors.forename: Anika
authors.initials: A
authors.lastname: Schmith
authors.forename: Sergej
authors.initials: S
authors.lastname: Herzog
authors.forename: Thomas
authors.initials: T
authors.lastname: Stach
authors.forename: Barbara
authors.initials: B
authors.lastname: Weissenmayer
authors.forename: Rupert
authors.initials: R
authors.lastname: Mutzel
mesh_terms: D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D013312:Stress, Physiological; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D015800:Protozoan Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D038341:Glycogen Synthase Kinases; D019703:Calcineurin; D002118:Calcium