Homolog of mammalian, voltage-gated calcium channels mediates yeast pheromone-stimulated Ca2+ uptake and exacerbates the cdc1(Ts) growth defect
Homolog of mammalian, voltage-gated calcium channels mediates yeast pheromone-stimulated Ca2+ uptake and exacerbates the cdc1(Ts) growth defect
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DOI：
10.1128/mcb.17.11.6339
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发表时间：
1997-11-01
影响因子：
5.3
通讯作者：
Garrett, S
中科院分区：
文献类型：
--
作者：
Paidhungat, M;Garrett, S
先前的研究将酵母（酿酒酵母）cdc1（Ts）生长缺陷归因于Mn 2+依赖性功能的丧失。在这份报告中，我们表明，cdc1（Ts）的温度敏感的增长也与细胞内Ca2+的增加。我们确定了两个隐性抑制剂的cdc1（Ts）的温度敏感的增长，阻止Ca2+的吸收和积累，这表明胞质Ca2+加剧或负责cdc1（Ts）的生长缺陷。cdc1（Ts）抑制基因之一是相同的基因，MID1，最近牵连在交配信息素刺激的Ca 2+摄取。对应于第二个抑制子的基因（CCH1）编码的蛋白质与高等真核生物质膜电压门控Ca2+通道的成孔亚基（α 1）具有显著的序列相似性。缺乏Mid1或Cch1蛋白的菌株表现出信息素诱导的Ca2+摄取的缺陷，因此在交配停滞时失去活力。mid1 Delta和cch1 Delta突变体也显示出对单价阳离子如Li+的耐受性降低，表明钙离子摄取在钙调神经磷酸酶依赖性离子应激反应中的作用。最后，mid1 Delta cch1 Delta双突变体，生理和遗传标准，相同的单突变体。这些和其他结果表明Mid1和Cch1是酵母Ca2+通道的组成部分，可以介导Ca2+的吸收，响应交配信息素，盐胁迫和Mn2+耗尽。
Previous studies attributed the yeast (Saccharomyces cerevisiae) cdc1(Ts) growth defect to loss of an Mn2+-dependent function. In this report we show that cdc1(Ts) temperature-sensitive growth is also associated with an increase in cytosolic Ca2+. We identified two recessive suppressors of the cdc1(Ts) temperature-sensitive growth which block Ca2+ uptake and accumulation, suggesting that cytosolic Ca2+ exacerbates or is responsible for the cdc1(Ts) growth defect. One of the cdc1(Ts) suppressors is identical to a gene, MID1, recently implicated in mating pheromone-stimulated Ca2+ uptake. The gene (CCH1) corresponding to the second suppressor encodes a protein that bears significant sequence similarity to the pore-forming subunit (alpha 1) of plasma membrane, voltage-gated Ca2+ channels from higher eukaryotes. Strains lacking Mid1 or Cch1 protein exhibit a defect in pheromone-induced Ca2+ uptake and consequently lose viability upon mating arrest. The mid1 Delta and cch1 Delta mutants also display reduced tolerance to monovalent cations such as Li+, suggesting a role for Ca2+ uptake in the calcineurin-dependent ion stress response. Finally, mid1 Delta cch1 Delta double mutants are, by both physiological and genetic criteria, identical to single mutants. These and other results suggest Mid1 and Cch1 are components of a yeast Ca2+ channel that may mediate Ca2+ uptake in response to mating pheromone, salt stress, and Mn2+ depletion.