Lopez F, Leube M, Gil-Mascarell R, Navarro-Aviñó J P, Serrano R
Instituto de Biología Molecular y Celular de Plantas, Universidad de Valencia-CSIC, Spain.
Mol Microbiol. 1999 Feb;31(4):1255-64. doi: 10.1046/j.1365-2958.1999.01267.x.
Inositol monophosphatases (IMPases) are lithium-sensitive enzymes that participate in the inositol cycle of calcium signalling and in inositol biosynthesis. Two open reading frames (YHR046c and YDR287w) with homology to animal and plant IMPases are present in the yeast genome. The two recombinant purified proteins were shown to catalyse inositol-1-phosphate hydrolysis sensitive to lithium and sodium. A double gene disruption had no apparent growth defect and was not auxotroph for inositol. Therefore, lithium effects in yeast cannot be explained by inhibition of IMPases and inositol depletion, as suggested for animal systems. Overexpression of yeast IMPases increased lithium and sodium tolerance and reduced the intracellular accumulation of lithium. This phenotype was blocked by a null mutation in the cation-extrusion ATPase encoded by the ENA1/PMR2A gene, but it was not affected by inositol supplementation. As overexpression of IMPases increased intracellular free Ca2+, it is suggested that yeast IMPases are limiting for the optimal operation of the inositol cycle of calcium signalling, which modulates the Ena1 cation-extrusion ATPase.
肌醇单磷酸酶（IMPases）是对锂敏感的酶，参与钙信号的肌醇循环和肌醇生物合成。酵母基因组中存在两个与动植物IMPases具有同源性的开放阅读框（YHR046c和YDR287w）。两种重组纯化蛋白显示出催化对锂和钠敏感的肌醇-1-磷酸水解。双基因破坏没有明显的生长缺陷，且对肌醇不具有营养缺陷型。因此，酵母中的锂效应不能像动物系统那样通过抑制IMPases和肌醇耗竭来解释。酵母IMPases的过表达增加了对锂和钠的耐受性，并减少了细胞内锂的积累。这种表型被ENA1/PMR2A基因编码的阳离子外排ATP酶的无效突变所阻断，但不受肌醇补充的影响。由于IMPases的过表达增加了细胞内游离Ca2+水平，因此有人提出酵母IMPases是钙信号肌醇循环最佳运作的限制因素，该循环调节Ena1阳离子外排ATP酶。
