An essential role of the yeast pheromone-induced Ca2+ signal is to activate calcineurin.
An essential role of the yeast pheromone-induced Ca2+ signal is to activate calcineurin.
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DOI：
10.1091/mbc.8.2.263
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发表时间：
1997-02
影响因子：
3.3
通讯作者：
J. Withee;J. Mulholland;R. Jeng;M. Cyert
中科院分区：
文献类型：
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作者：
J. Withee;J. Mulholland;R. Jeng;M. Cyert
先前的研究表明，在野生型（MATa）细胞中，α -因子导致细胞质Ca2+的必要升高。我们发现钙调磷酸酶，钙调蛋白依赖蛋白磷酸酶，是Ca2+信号的一个靶点。钙调磷酸酶突变体在与交配信息素一起孵育时失去生存能力，而在缺乏Ca（2+）的培养基中，过量产生组成活性（不依赖Ca(2+)）钙调磷酸酶可以提高暴露于信息素的野生型细胞的生存能力。因此，信息素诱导的细胞质Ca2+升高的一个重要后果是钙调磷酸酶的激活。尽管钙调磷酸酶抑制酵母细胞内Ca2+的隔离，但无论是细胞外Ca2+的增加还是液泡Ca2+运输的缺陷，都不能绕过信息素反应过程中对钙调磷酸酶的需求。这些观察结果表明，钙调磷酸酶在信息素反应中的基本功能可能不同于其对细胞内Ca2+水平的调节。不经历信息素诱导的细胞周期阻滞（fus3, far1）的突变体在信息素治疗期间对钙调磷酸酶的依赖性降低。因此，在长时间暴露于信息素的酵母细胞中，尤其是在信息素诱导的生长停滞条件下，钙调磷酸酶是必不可少的。信息素处理细胞的超微结构检查表明，钙调磷酸酶缺乏细胞的空泡形态异常，提示在信息素反应过程中，钙调磷酸酶可能需要维持适当的空泡结构或功能。
Previous studies showed that, in wild-type (MATa) cells, alpha-factor causes an essential rise in cytosolic Ca2+. We show that calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, is one target of this Ca2+ signal. Calcineurin mutants lose viability when incubated with mating pheromone, and overproduction of constitutively active (Ca(2+)-independent) calcineurin improves the viability of wild-type cells exposed to pheromone in Ca(2+)-deficient medium. Thus, one essential consequence of the pheromone-induced rise in cytosolic Ca2+ is activation of calcineurin. Although calcineurin inhibits intracellular Ca2+ sequestration in yeast cells, neither increased extracellular Ca2+ nor defects in vacuolar Ca2+ transport bypasses the requirement for calcineurin during the pheromone response. These observations suggest that the essential function of calcineurin in the pheromone response may be distinct from its modulation of intracellular Ca2+ levels. Mutants that do not undergo pheromone-induced cell cycle arrest (fus3, far1) show decreased dependence on calcineurin during treatment with pheromone. Thus, calcineurin is essential in yeast cells during prolonged exposure to pheromone and especially under conditions of pheromone-induced growth arrest. Ultrastructural examination of pheromone-treated cells indicates that vacuolar morphology is abnormal in calcineurin-deficient cells, suggesting that calcineurin may be required for maintenance of proper vacuolar structure or function during the pheromone response.