title: Spatial control of calcineurin in response to heat shock in fission yeast.
abstract: In fission yeast, Ppb1, the Ca2+/calmodulin-dependent protein phosphatase calcineurin regulates multiple biological processes, such as cytokinesis, Ca2+-homeostasis, membrane trafficking and cell wall integrity. Calcineurin dephosphorylates the Prz1 transcription factor, leading to its nuclear translocation and gene expression under the control of CDRE (calcineurin-dependent response element). Although the calcineurin-mediated spatial control of downstream transcription factors has been intensively studied in many organisms, less is known about the spatial regulation of calcineurin on stresses. Here, we show that heat shock stimulates calcineurin-dependent nuclear translocation of Prz1 and CDRE-dependent gene expression. Notably, calcineurin exhibited a dramatic change in subcellular localization, translocating from diffuse cytoplasmic to dot-like structures on heat shock. The calcineurin dots colocalized with Dcp2 or Pabp, the constituent of P-bodies or stress granules, respectively, thus suggesting that calcineurin is a component of RNA granules under heat shock. Importantly, the calcineurin inhibitor FK506 markedly inhibited the accumulation of calcineurin granules, whereas the constitutively active calcineurin strongly accumulated in the granules on heat shock, suggesting that phosphatase activity is important for calcineurin localization. Notably, the depletion of calcineurin induced a rapid appearance of Nrd1- and Pabp-positive RNA granules. The possible roles of calcineurin in response to heat shock will be discussed.
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Higa
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.forename: Kanako
authors.initials: K
authors.lastname: Hagihara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kitai
authors.forename: Akira
authors.initials: A
authors.lastname: Doi
authors.forename: Rie
authors.initials: R
authors.lastname: Nagasoko
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satoh
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
mesh_terms: D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism*; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression; D018869:Heat-Shock Response; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012261:Ribonucleoproteins / Q000378:metabolism* / Q000648:ultrastructure; D012568:Schizosaccharomyces / Q000378:metabolism / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; C508496:Dcp2 protein, S pombe; D011500:Protein Synthesis Inhibitors; C000593219:Prz1 protein, S pombe; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C491210:nrd1 protein, S pombe; D003513:Cycloheximide; D019703:Calcineurin; D016559:Tacrolimus