Conservation and divergence of protein pathways in the vertebrate heart.

TitleConservation and divergence of protein pathways in the vertebrate heart.
Publication TypeJournal Article
Year of Publication2019
AuthorsFederspiel, JD, Tandon, P, Wilczewski, CM, Wasson, L, Herring, LE, Venkatesh, SS, Cristea, IM, Conlon, FL
JournalPLoS Biol
Date Published2019 Sep
KeywordsAnimals, Cell Cycle, Evolution, Molecular, Female, Heart, Heart Diseases, Humans, Mass Spectrometry, Mice, Models, Cardiovascular, Myocardium, Proteome, Sus scrofa, Xenopus laevis, Xenopus Proteins

<p>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.</p>

Alternate JournalPLoS Biol
PubMed ID31490923
PubMed Central IDPMC6750614
Grant ListR01 HD089275 / HD / NICHD NIH HHS / United States
R01 HL127640 / HL / NHLBI NIH HHS / United States
R01 HL135007 / HL / NHLBI NIH HHS / United States