A Mighty Small Heart: The Cardiac Proteome of AdultDrosophila melanogaster

摘要

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 ina recent Drosophila peptide compendium. PeptideClassifieranalysis was further used to map peptides to specific gene-models. 1872 peptidesprovide valuable information about protein isoform groups whereas a further 3112uniquely identify specific protein isoforms and may be used as aheart-associated peptide resource for quantitative proteomic approaches based onmultiple-reaction monitoring. In summary, identification ofexcitation-contraction protein landmarks, orthologues of proteins associatedwith cardiovascular defects, and conservation of protein ontologies, providestestimony to the heart-like character of the Drosophila cardiactube and to the utility of proteomics as a complement to the power of geneticsin this growing model of human heart disease.