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Spatial control of calcineurin in response to heat shock in fission yeast

机译:裂变酵母中热激响应钙调神经磷酸酶的空间控制

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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.
机译:在裂变酵母Ppb1中,Ca2 + /钙调蛋白依赖性蛋白磷酸酶钙调磷酸酶调节多种生物过程,例如胞质分裂,Ca2 +稳态,膜运输和细胞壁完整性。钙调神经磷酸酶使Prz1转录因子去磷酸化,导致其核易位和基因表达在CDRE(钙调神经磷酸酶依赖性反应元件)的控制下。尽管钙调神经磷酸酶介导的下游转录因子的空间控制已在许多生物体中得到了深入研究,但关于钙调神经磷酸酶在压力下的空间调控知之甚少。在这里,我们显示热休克刺激钙调神经磷酸依赖的Prz1和CDRE依赖的基因表达的核易位。值得注意的是,钙调神经磷酸酶在亚细胞定位中表现出显着变化,在热激时从弥散性细胞质转变为点状结构。钙调神经磷酸酶点分别与Dcp2或Pabp(P体或应激颗粒的组成部分)共定位,因此表明钙调神经磷酸酶是热激下RNA颗粒的组成部分。重要的是,钙调神经磷酸酶抑制剂FK506显着抑制了钙调神经磷酸酶颗粒的积累,而热休克时,组成型活性钙调神经磷酸酶强烈地积聚在颗粒中,这表明磷酸酶活性对于钙调神经磷酸酶的定位很重要。值得注意的是,钙调神经磷酸酶的耗尽导致Nrd1和Pabp阳性RNA颗粒快速出现。将讨论钙调神经磷酸酶对热休克的可能作用。

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