A systematic analysis of protein palmitoylation in Caenorhabditis elegans.
A systematic analysis of protein palmitoylation in Caenorhabditis elegans.
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DOI：
10.1186/1471-2164-15-841
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发表时间：
2014-10-02
期刊：
影响因子：
4.4
通讯作者：
Morgan A
中科院分区：
文献类型：
--
作者：
Edmonds MJ;Morgan A
棕榈酰化是一种可逆的蛋白质翻译后修饰，其涉及将棕榈酸添加到半胱氨酸残基。棕榈酰化由棕榈酰-酰基转移酶（PAT）的DHHC家族催化，并且可逆性由棕榈酰-蛋白硫酯酶（PPT）赋予。编码这两类酶的基因突变与人类疾病有关，特别是神经系统疾病，突出了它们的重要性。尽管酵母研究在发现PAT方面发挥了关键作用，但棕榈酰化尚未在关键动物模型秀丽隐杆线虫中进行研究。分析了C. elegans基因组鉴定了15个PAT，使用DHHC富含半胱氨酸的结构域，和两个PPT，通过同源性。12个未分类的PAT使用dhhc-x系统正式命名。对这些棕榈酰化酶的基因组数据以及酵母、果蝇和人类的基因组数据进行了整理和分析，以预测C。优雅所有可用的C。分析了含有棕榈酰化酶突变的线虫菌株，并产生了针对PAT或PPT基因的RNA干扰（RNAi）饲养质粒的完整文库。为了测试可能的冗余，针对选择的密切相关的PAT和两个PPT进行双重RNAi。筛选动物的表型，包括大小，寿命和感觉和运动神经元功能。尽管在个别突变体或RNAi处理中观察到一些显著差异，但总体上对这些表型几乎没有影响，这表明在蠕虫的棕榈酰化网络中存在遗传缓冲。本研究首次报道了C. elegans使用在硅片和在体内的方法，并打开了这个关键的模式生物，为进一步详细的研究棕榈酰化在未来。本文的在线版本（doi：10.1186/1471-2164-15-841）包含补充材料，可供授权用户使用。
Palmitoylation is a reversible post-translational protein modification which involves the addition of palmitate to cysteine residues. Palmitoylation is catalysed by the DHHC family of palmitoyl-acyl transferases (PATs) and reversibility is conferred by palmitoyl-protein thioesterases (PPTs). Mutations in genes encoding both classes of enzymes are associated with human diseases, notably neurological disorders, underlining their importance. Despite the pivotal role of yeast studies in discovering PATs, palmitoylation has not been studied in the key animal model Caenorhabditis elegans. Analysis of the C. elegans genome identified fifteen PATs, using the DHHC cysteine-rich domain, and two PPTs, by homology. The twelve uncategorised PATs were officially named using a dhhc-x system. Genomic data on these palmitoylation enzymes and those in yeast, Drosophila and humans was collated and analysed to predict properties and relationships in C. elegans. All available C. elegans strains containing a mutation in a palmitoylation enzyme were analysed and a complete library of RNA interference (RNAi) feeding plasmids against PAT or PPT genes was generated. To test for possible redundancy, double RNAi was performed against selected closely related PATs and both PPTs. Animals were screened for phenotypes including size, longevity and sensory and motor neuronal functions. Although some significant differences were observed with individual mutants or RNAi treatment, in general there was little impact on these phenotypes, suggesting that genetic buffering exists within the palmitoylation network in worms. This study reports the first characterisation of palmitoylation in C. elegans using both in silico and in vivo approaches, and opens up this key model organism for further detailed study of palmitoylation in future. The online version of this article (doi:10.1186/1471-2164-15-841) contains supplementary material, which is available to authorized users.
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