A mighty small heart: the cardiac proteome of adult Drosophila melanogaster.

A mighty small heart: the cardiac proteome of adult Drosophila melanogaster.
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DOI:
10.1371/journal.pone.0018497
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发表时间:
2011-04-25
期刊:
影响因子:
3.7
通讯作者:
Foster DB
Foster DB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cammarato A;Ahrens CH;Alayari NN;Qeli E;Rucker J;Reedy MC;Zmasek CM;Gucek M;Cole RN;Van Eyk JE;Bodmer R;O'Rourke B;Bernstein SI;Foster DB

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黑腹果蝇正在成为研究心脏病的一个强有力的模型系统。建立果蝇心脏的肽和蛋白质图谱是实施蛋白质网络研究的核心,这将使我们能够评估果蝇心脏发病机制的标志,并在系统水平上衡量人类疾病机制的保守程度。使用凝胶-LC-MS/MS方法,我们确定了1228个蛋白质簇从145个解剖的成年苍蝇心脏。收缩,细胞结构和线粒体蛋白质是最丰富的果蝇心管的电子显微镜照片一致。功能/本体富集分析进一步表明,参与糖酵解、Ca 2+结合、氧化还原和G蛋白信号传导等过程的蛋白质也被过度表达。与小鼠心脏蛋白质组的比较显示,在分子功能,生物过程和细胞成分的水平上的保护。现存的肽组包括5169种不同的心脏相关肽,其中1293种(25%)在最近的果蝇肽纲要中未被鉴定。进一步使用PeptideClassifier分析将肽映射到特定基因模型。1872种肽提供了关于蛋白质同种型组的有价值的信息,而另外3112种肽独特地鉴定了特定的蛋白质同种型,并且可以用作基于多反应监测的定量蛋白质组学方法的心脏相关肽资源。总之,兴奋-收缩蛋白标志物的鉴定,与心血管缺陷相关的蛋白质的直向同源物,以及蛋白质本体的保护,为果蝇心管的心脏样特征和蛋白质组学在这种不断增长的人类心脏病模型中作为遗传学力量的补充的实用性提供了证据。
Drosophila melanogaster is emerging as a powerful model system for the study of cardiac disease. Establishing peptide and protein maps of the Drosophila heart is central to implementation of protein network studies that will allow us to assess the hallmarks of Drosophila heart pathogenesis and gauge the degree of conservation with human disease mechanisms on a systems level. Using a gel-LC-MS/MS approach, we identified 1228 protein clusters from 145 dissected adult fly hearts. Contractile, cytostructural and mitochondrial proteins were most abundant consistent with electron micrographs of the Drosophila cardiac tube. Functional/Ontological enrichment analysis further showed that proteins involved in glycolysis, Ca2+-binding, redox, and G-protein signaling, among other processes, are also over-represented. Comparison with a mouse heart proteome revealed conservation at the level of molecular function, biological processes and cellular components. The subsisting peptidome encompassed 5169 distinct heart-associated peptides, of which 1293 (25%) had not been identified in a recent Drosophila peptide compendium. PeptideClassifier analysis was further used to map peptides to specific gene-models. 1872 peptides provide valuable information about protein isoform groups whereas a further 3112 uniquely identify specific protein isoforms and may be used as a heart-associated peptide resource for quantitative proteomic approaches based on multiple-reaction monitoring. In summary, identification of excitation-contraction protein landmarks, orthologues of proteins associated with cardiovascular defects, and conservation of protein ontologies, provides testimony to the heart-like character of the Drosophila cardiac tube and to the utility of proteomics as a complement to the power of genetics in this growing model of human heart disease.
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