A Mighty Small Heart: The Cardiac Proteome of Adult Drosophila melanogaster

Cammarato, Anthony; Ahrens, Christian H.; Alayari, Nakissa N.; Qeli, Ermir; Rucker, Jasma; Reedy, Mary C.; Zmasek, Christian M.; Guček, Marjan; Cole, Robert N.; Eyk, Jennifer E. Van; Bodmer, Rolf; O’Rourke, Brian; Bernstein, Sanford I.; Foster, D. Brian

doi:10.1371/journal.pone.0018497

Cited by 83 publications

(81 citation statements)

References 42 publications

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“…Our results identified 502 protein clusters from purified cardiomyocyte nuclei. We note that this number of proteins is less than reported for cardiac protein profiling in the adult fly or mouse heart (Bousette et al, 2009;Cammarato et al, 2011). However, there are several possible reasons for this discrepancy.…”

Section: Cardiac Profilingcontrasting

confidence: 58%

Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT)

Amin

Greco

et al. 2014

Development

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The proper dissection of the molecular mechanisms governing the specification and differentiation of specific cell types requires isolation of pure cell populations from heterogeneous tissues and whole organisms. Here, we describe a method for purification of nuclei from defined cell or tissue types in vertebrate embryos using INTACT (isolation of nuclei tagged in specific cell types). This method, previously developed in plants, flies and worms, utilizes in vivo tagging of the nuclear envelope with biotin and the subsequent affinity purification of the labeled nuclei. In this study we successfully purified nuclei of cardiac and skeletal muscle from Xenopus using this strategy. We went on to demonstrate the utility of this approach by coupling the INTACT approach with liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic methodologies to profile proteins expressed in the nuclei of developing hearts. From these studies we have identified the Xenopus orthologs of 12 human proteins encoded by genes, which when mutated in human lead to congenital heart disease. Thus, by combining these technologies we are able to identify tissue-specific proteins that are expressed and required for normal vertebrate organ development.

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Section: Cardiac Profilingcontrasting

confidence: 58%

Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT)

Amin

Greco

et al. 2014

Development

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“…However, the complexity of data obtained from proteomic studies makes translation of putative biomarkers into clinically useful prognostic tools difficult. As has been reviewed extensively elsewhere, proteomics has been successfully applied as a discovery tool to CVD in plasma, urine, and tissue [199][200][201][202] in the context of both animal models aimed at understanding cardiac function and development 203 and human biomarkers of atherosclerosis, 204 dyslipidemia, 205 and cardiometabolic disease. 206 Proteomics has also been applied in the context of nutritional studies to identify biomarkers of diet and nutritional status.…”

Section: Proteomicsmentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

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Abstract-Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. The interpretation and scope of nutrigenomics may vary, but it can be thought to encompass the spectrum of nutritional genomics research, including classic nutrigenetics studies of gene-diet interactions and molecular nutrition, in vitro and in vivo models, human nutrition studies, and the application of largescale, unbiased studies using high-throughput "omics" techniques to study the effects of nutrients on the body. 6 As the Figure shows, diet and the genome may influence cardiometabolic health through a variety of interconnected intermediates, perturbations in which can be measured through omics technologies, including RNA expression (transcriptome), epigenetic modifications (epigenome), metabolites (metabolome), lipids (lipidome), proteins (proteome), and resident microbial communities (microbiome). Although it is clear that both nutrients and genes play a distinct role in determining health, the complex interactions among genes, diet, and downstream networks are not well understood. The application of nutrigenomics approaches to questions of human health and disease is an important component in understanding the complexities of the interplay between basic metabolic processes and externalThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 22, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The...

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“…However, similar proteomic studies of internal cell populations have been more difficult and are usually only partially represented in proteomes of whole organs owing to signal dilution (e.g., refs. [11][12][13][14][15][16].…”

mentioning

confidence: 99%

The protein expression landscape of the Arabidopsis root

Petricka

Schauer

Megraw

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

157

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Because proteins are the major functional components of cells, knowledge of their cellular localization is crucial to gaining an understanding of the biology of multicellular organisms. We have generated a protein expression map of the Arabidopsis root providing the identity and cell type-specific localization of nearly 2,000 proteins. Grouping proteins into functional categories revealed unique cellular functions and identified cell type-specific biomarkers. Cellular colocalization provided support for numerous protein-protein interactions. With a binary comparison, we found that RNA and protein expression profiles are weakly correlated. We then performed peak integration at cell type-specific resolution and found an improved correlation with transcriptome data using continuous values. We performed GeLC-MS/MS (in-gel tryptic digestion followed by liquid chromatography-tandem mass spectrometry) proteomic experiments on mutants with ectopic and no root hairs, providing complementary proteomic data. Finally, among our root hair-specific proteins we identified two unique regulators of root hair development.plant proteome | cell-type expression | FACS | RNA-protein correlation | root hair mutant M ulticellular organisms use specialized cell types to perform activities that are integral to their function. Cellular tasks are usually achieved by proteins, which act in signaling cascades, provide structural support, and catalyze enzymatic reactions vital to growth and metabolism. Knowledge of protein cellular localization and abundance using proteomic approaches is thus crucial to our understanding of biological systems (1, 2). Proteome data can be visually represented in a map, which highlights the spatial relationships of proteins at the level of cell type, tissue, or organ. Proteome maps are useful representations of the complex "building plan" of a biological system and also serve as valuable tools for the discovery of new cellular functions (2, 3). Proteomic studies of single cell populations isolated from a variety of multicellular organisms have recently been achieved, including the oocytes of worms and mice (4-6); pollen grains (consisting of two sperm and one vegetative cell) and stomatal guard cells of plants (7,8); and sperm cells of mice and flies (9, 10). These cell types were relatively accessible because they either reside on the surface and can be purified in large quantities using biochemical fractionation (e.g., guard cells) or are large and can easily be collected (e.g., Caenorhabditis elegans oocytes). However, similar proteomic studies of internal cell populations have been more difficult and are usually only partially represented in proteomes of whole organs owing to signal dilution (e.g., refs. 11-16).The Arabidopsis thaliana root is an excellent model for investigating cellular functions internal to an organ because it is transparent, radially symmetric, and cell types can be isolated by FACS to allow molecular profiling (17). The goal of this study was to investigate cell-type function by genera...

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A Mighty Small Heart: The Cardiac Proteome of Adult Drosophila melanogaster

Cited by 83 publications

References 42 publications

Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT)

Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT)

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

The protein expression landscape of the Arabidopsis root

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