Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases.
Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases.
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DOI：
10.1083/jcb.124.3.351
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发表时间：
1994-02
期刊：
影响因子：
--
通讯作者：
Fink GR
中科院分区：
文献类型：
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作者：
Cunningham KW;Fink GR
Ca2+ ATP酶消耗细胞质中的Ca2+离子，对细胞内Ca2+稳态至关重要。酿酒酵母的PMC1基因编码一种液泡膜蛋白，与哺乳动物细胞的质膜Ca2+ ATP酶（PMCAs）有40%的同源性。缺乏PMC1的突变体在标准培养基中生长良好，但将Ca2+以野生型水平的20%螯合到液泡中。pmc 1无效突变体不能在含有高水平Ca 2+的培养基中生长，表明PMC1在Ca 2+耐受中的作用。添加的Ca 2+的生长抑制作用需要激活钙调磷酸酶，一种Ca 2+和钙调蛋白依赖性蛋白磷酸酶。钙调神经磷酸酶A或B亚基或抑制性化合物FK 506和环孢菌素A的突变恢复pmc 1突变体在高Ca 2+培养基中的生长。此外，生长恢复的隐性突变，使高亲和力的钙（2+）结合位点的钙调蛋白。这种突变的钙调素显然失去了在体内激活钙调磷酸酶的能力。这些结果表明，激活钙调磷酸酶的Ca 2+和钙调蛋白可以负面影响酵母生长。由PMR 1基因编码的第二种Ca2+ ATP酶同源物与PMC1一起作用，即使在标准（低Ca2+）条件下也能防止钙调磷酸酶的致死性激活。我们建议，这些Ca2+ ATP酶同系物是必不可少的酵母细胞质中耗尽的Ca2+离子，在升高的浓度，抑制酵母生长，通过不适当的激活钙调磷酸酶。
Ca2+ ATPases deplete the cytosol of Ca2+ ions and are crucial to cellular Ca2+ homeostasis. The PMC1 gene of Saccharomyces cerevisiae encodes a vacuole membrane protein that is 40% identical to the plasma membrane Ca2+ ATPases (PMCAs) of mammalian cells. Mutants lacking PMC1 grow well in standard media, but sequester Ca2+ into the vacuole at 20% of the wild-type levels. pmc1 null mutants fail to grow in media containing high levels of Ca2+, suggesting a role of PMC1 in Ca2+ tolerance. The growth inhibitory effect of added Ca2+ requires activation of calcineurin, a Ca2+ and calmodulin-dependent protein phosphatase. Mutations in calcineurin A or B subunits or the inhibitory compounds FK506 and cyclosporin A restore growth of pmc1 mutants in high Ca2+ media. Also, growth is restored by recessive mutations that inactivate the high-affinity Ca(2+)-binding sites in calmodulin. This mutant calmodulin has apparently lost the ability to activate calcineurin in vivo. These results suggest that activation of calcineurin by Ca2+ and calmodulin can negatively affect yeast growth. A second Ca2+ ATPase homolog encoded by the PMR1 gene acts together with PMC1 to prevent lethal activation of calcineurin even in standard (low Ca2+) conditions. We propose that these Ca2+ ATPase homologs are essential in yeast to deplete the cytosol of Ca2+ ions which, at elevated concentrations, inhibits yeast growth through inappropriate activation of calcineurin.