vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.
vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.
复制标题
酿酒酵母的 vph6 突变体需要钙调神经磷酸酶才能生长，并且在液泡 H(+)-ATP 酶组装方面存在缺陷。
DOI：
10.1093/genetics/141.3.833
复制
发表时间：
1995
期刊：
影响因子：
3.3
通讯作者：
Heitman,J
中科院分区：
文献类型：
--
作者：
Hemenway,CS;Dolinski,K;Cardenas,ME;Hiller,MA;Jones,EW;Heitman,J
我们鉴定了一种对环孢菌素 A (CsA) 和 FK506 过敏的酿酒酵母突变株，这两种免疫抑制剂可抑制钙调神经磷酸酶（一种丝氨酸-苏氨酸特异性磷酸酶 (PP2B)）。 CsA-FK506 敏感表型由单个核突变（命名为 cev1）（对于生存至关重要的钙调神经磷酸酶）负责。肽基脯氨酰顺反异构酶亲环蛋白 A 和 FKBP12 分别介导 cev1 突变株中的 CsA 和 FK506 毒性。我们证明cev1是VPH6基因的等位基因，并且vph6突变株无法组装液泡H(+)-ATP酶(V-ATP酶)。 VPH6 基因定位在 VIII 号染色体上，预计编码 181 个氨基酸 (21 kD) 的蛋白质，与其他已知蛋白质没有同一性。我们发现钙调神经磷酸酶对于许多具有 V-ATP 酶功能或液泡酸化缺陷的突变菌株的生存至关重要。此外，我们发现钙调磷酸酶可响应葡萄糖调节细胞外酸化，我们认为这是通过钙调磷酸酶对质膜 H(+)-ATPase PMA1 的调节而发生的。综上所述，我们的研究结果表明钙调神经磷酸酶在阳离子运输和体内平衡的调节中发挥着普遍作用。
We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 for calcineurin essential for viability, is responsible for the CsA-FK506-sensitive phenotype. The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, respectively, mediate CsA and FK506 toxicity in the cev1 mutant strain. We demonstrate that cev1 is an allele of the VPH6 gene and that vph6 mutant strains fail to assemble the vacuolar H(+)-ATPase (V-ATPase). The VPH6 gene was mapped on chromosome VIII and is predicted to encode a 181-amino acid (21 kD) protein with no identity to other known proteins. We find that calcineurin is essential for viability in many mutant strains with defects in V-ATPase function or vacuolar acidification. In addition, we find that calcineurin modulates extracellular acidification in response to glucose, which we propose occurs via calcineurin regulation of the plasma membrane H(+)-ATPase PMA1. Taken together, our findings suggest calcineurin plays a general role in the regulation of cation transport and homeostasis.