Li Jianrong, Zhang Bing, Ma Tianyu, Wang Honggang, Zhang Biao, Yu Qilin, Li Mingchun
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Science, Nankai University, Tianjin, 300071, People's Republic of China.
Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
Mycopathologia. 2017 Aug;182(7-8):609-623. doi: 10.1007/s11046-017-0138-4. Epub 2017 May 13.
Inositol polyphosphates are a family of inositol derivatives and ubiquitously distributed in various organisms. Their generation is catalyzed by inositol polyphosphate multikinases, which play essential roles in abundant cellular processes. However, little is known about the kinds and functions of inositol polyphosphate multikinases in the important fungal pathogen, C. albicans. In this study, we identified a C. albicans inositol polyphosphate multikinase, Ipk2. This kinase shares the conserved IPK domain and localizes in the nucleus. A strain with controllable expression of IPK2 was constructed using the inducible promoter of MET3. Down-regulation of IPK2 by addition of methionine and cysteine enhanced the ability of hyphal development, increased expression of hypha-specific genes and promoted transport of hypha-specific factors. Moreover, this down-regulation rendered increase in cytoplasmic calcium levels but decrease in cellular total calcium contents, indicating its role in regulation of calcium homeostasis. Assays of secretion and macrophage killing further demonstrated that Ipk2 negatively regulated secretion of degradative enzymes and damage to macrophages. This study sheds a novel light on the functions of inositol polyphosphate multikinases in fungal organisms.
肌醇多磷酸是肌醇衍生物家族，广泛分布于各种生物体中。它们的生成由肌醇多磷酸多激酶催化，这些激酶在众多细胞过程中发挥着重要作用。然而，对于重要的真菌病原体白色念珠菌中肌醇多磷酸多激酶的种类和功能却知之甚少。在本研究中，我们鉴定出一种白色念珠菌肌醇多磷酸多激酶Ipk2。该激酶具有保守的IPK结构域并定位于细胞核。利用MET3的诱导型启动子构建了IPK2表达可调控的菌株。通过添加蛋氨酸和半胱氨酸下调IPK2增强了菌丝发育能力，增加了菌丝特异性基因的表达，并促进了菌丝特异性因子的转运。此外，这种下调导致细胞质钙水平升高但细胞总钙含量降低，表明其在调节钙稳态中的作用。分泌和巨噬细胞杀伤试验进一步证明Ipk2对降解酶的分泌和对巨噬细胞的损伤具有负调控作用。本研究为肌醇多磷酸多激酶在真菌生物体中的功能提供了新的见解。
