Abstract:
Effects of temperature on biological processes are complex. Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change.
摘要:
温度对生物过程的影响是复杂的。与具有不同的单个温度曲线的不同酶促反应相比,扩散受到的影响较小。因此,热波动对体温很大程度上由环境温度决定的放热生物构成了严峻的挑战。在分子水平上,人们对细胞如何应对温度变化的无数破坏性影响知之甚少。在这里,我们表明,具有O连接的GlcNAc(O-GlcNAc)的蛋白质的核质翻译后修饰与环境温度密切相关,从昆虫果蝇到线虫秀丽隐杆线虫到鱼类Daniorerio。调节似乎发生在仅有的两种酶的活性水平上,O-GlcNAc转移酶和O-GlcNAcase,添加和删除,分别,这种在细胞核和细胞质中的翻译后修饰。通过对黑腹线虫和秀丽隐杆线虫的遗传方法,我们证明了高水平的这种翻译后修饰对于在高温下成功开发的重要性。因为不同途径中的许多细胞质和核蛋白是O-GlcNAc靶标,这种修改的温度依赖性调节可能有助于响应热变化而对细胞过程进行有效的协调调节。