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PLoS Biol 2019 Sep 06;179:e3000437. doi: 10.1371/journal.pbio.3000437.
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Conservation and divergence of protein pathways in the vertebrate heart.

Federspiel JD , Tandon P , Wilczewski CM , Wasson L , Herring LE , Venkatesh SS , Cristea IM , Conlon FL .

Heart disease is the leading cause of death in the western world. Attaining a mechanistic understanding of human heart development and homeostasis and the molecular basis of associated disease states relies on the use of animal models. Here, we present the cardiac proteomes of 4 model vertebrates with dual circulatory systems: the pig (Sus scrofa), the mouse (Mus musculus), and 2 frogs (Xenopus laevis and Xenopus tropicalis). Determination of which proteins and protein pathways are conserved and which have diverged within these species will aid in our ability to choose the appropriate models for determining protein function and to model human disease. We uncover mammalian- and amphibian-specific, as well as species-specific, enriched proteins and protein pathways. Among these, we find and validate an enrichment in cell-cycle-associated proteins within Xenopus laevis. To further investigate functional units within cardiac proteomes, we develop a computational approach to profile the abundance of protein complexes across species. Finally, we demonstrate the utility of these data sets for predicting appropriate model systems for studying given cardiac conditions by testing the role of Kielin/chordin-like protein (Kcp), a protein found as enriched in frog hearts compared to mammals. We establish that germ-line mutations in Kcp in Xenopus lead to valve defects and, ultimately, cardiac failure and death. Thus, integrating these findings with data on proteins responsible for cardiac disease should lead to the development of refined, species-specific models for protein function and disease states.

PubMed ID: 31490923
PMC ID: PMC6750614
Article link: PLoS Biol
Grant support: [+]

Species referenced: Xenopus Xenopus tropicalis
Genes referenced: agpat2 akt2 banf1 bmp2 bscl2 cadm1 cadm2 cadm3 cadm4 cbl cenpv creld1 csnk2a1 csnk2a2 csnk2b egfr eml4 erh fbn1 fga fgb fgg gpaa1 hcfc1 ids ik il6st itgav itgb5 kcp lif lifr lpin1 mapk1 mapre1 mcts1 micos13 mre11 mvp nbn nelfa nelfb nelfcd nelfe nup107 nup133 nup160 nup54 nup62 nup98 ogt parp3 pcna pds5a pex1 pex26 pex6 pfdn1 pfdn2 pfdn5 pigk pigs pigt pigu plaur ppm1a ppp1r12a prkaa2 prkab2 prmt1 psmb1 psmb3 psmd6 rad50 rae1 ranbp1 rbbp7 rbfox2 rbm20 sec13 sh3glb1 sh3kbp1 smc3 snx18 sumo1 tpr trak1 trak2 tubg1 uba2 ube2l3 vbp1 vps11 vps16 vps18 vps33a xrcc5 xrcc6 ywhae

Disease Ontology terms: arrhythmogenic right ventricular cardiomyopathy [+]
Phenotypes: Xla Wt + bmp2 (Fig S22 C) [+]

Article Images: [+] show captions
References [+] :
Bagwan, Comprehensive Quantification of the Modified Proteome Reveals Oxidative Heart Damage in Mitochondrial Heteroplasmy. 2018, Pubmed