Chen Di, Zhang Jiuli, Minnerly Justin, Kaul Tiffany, Riddle Donald L, Jia Kailiang
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
Department of Biological Sciences, Florida Atlantic University, Jupiter, Florida, United States of America.
PLoS Genet. 2014 Oct 16;10(10):e1004699. doi: 10.1371/journal.pgen.1004699. eCollection 2014 Oct.
The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.
秀丽隐杆线虫的 dauer 幼虫是一种兼性滞育状态。已有报道称存在影响 dauer 信号转导和形态发生的突变。其中，大多数导致 dauer 幼虫组成型形成的突变是温度敏感型（ts）。daf - 31 突变体是在遗传筛选中分离得到的，该筛选旨在寻找无条件形成 dauer 和 dauer 样幼虫的新型且代表性不足的突变体类别。dauer 样幼虫在发育过程中停滞，具有一些但并非全部正常 dauer 的特征。我们在此表明，daf - 31 突变体在饥饿条件下形成 dauer 样幼虫，但对 SDS 处理敏感。此外，daf - 31 突变体的代谢转变为脂肪积累。我们克隆了 daf - 31 基因，它编码 arrest - defective - 1 蛋白（ARD1）的直系同源物，ARD1 是主要的 Nα - 乙酰转移酶（NatA）的催化亚基。一个 daf - 31 启动子::GFP 报告基因表明 daf - 31 在包括神经元、咽部、肠道和皮下细胞在内的多个组织中表达。有趣的是，daf - 31 的过表达增强了 daf - 2 突变体的长寿表型，这依赖于叉头转录因子（FOXO）DAF - 16。我们证明 daf - 31 的过表达刺激了 DAF - 16 的转录活性，而不影响其亚细胞定位。这些数据揭示了 NatA 在控制秀丽隐杆线虫生活史中的重要作用，以及 ARD1 与 FOXO 转录因子之间的新型相互作用，这可能有助于理解 ARD1 在哺乳动物中的功能。
