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Your search keyword '"Yates, John R."' showing total 22 results
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22 results on '"Yates, John R."'

1. Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function

Author

Wortham, Matthew, Benthuysen, Jacqueline R, Wallace, Martina, Savas, Jeffrey N, Mulas, Francesca, Divakaruni, Ajit S, Liu, Fenfen, Albert, Verena, Taylor, Brandon L, Sui, Yinghui, Saez, Enrique, Murphy, Anne N, Yates, John R, Metallo, Christian M, and Sander, Maike

Subjects
Biochemistry and Cell Biology, Biological Sciences, Diabetes, Nutrition, Biotechnology, Digestive Diseases, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Aetiology, Metabolic and endocrine, Aging, Animals, Carbon, Cell Respiration, Cellular Senescence, Citric Acid Cycle, Female, Gene Expression Regulation, Glucose, Insulin Secretion, Insulin-Secreting Cells, Male, Metabolomics, Mice, Inbred C57BL, Proteome, Proteomics, SILAM MudPIT mass spectrometry, TCA cycle, aging, amplifying pathway, insulin secretion, isotope tracing, quantitative proteomics, triggering pathway, β cell, β cell maturation, Medical Physiology, Biological sciences
Abstract

Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from 1-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides an in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in β cell function.

Published
2018

2. S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson’s Disease Models

Author

Oh, Chang-Ki, Sultan, Abdullah, Platzer, Joseph, Dolatabadi, Nima, Soldner, Frank, McClatchy, Daniel B, Diedrich, Jolene K, Yates, John R, Ambasudhan, Rajesh, Nakamura, Tomohiro, Jaenisch, Rudolf, and Lipton, Stuart A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Brain Disorders, Stem Cell Research - Induced Pluripotent Stem Cell, Aging, Parkinson's Disease, Stem Cell Research, Neurosciences, Neurodegenerative, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell - Human, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Humans, Induced Pluripotent Stem Cells, Mice, Mitochondria, Mitophagy, Mutation, Neurons, Parkinson Disease, Protein Kinases, Ubiquitin-Protein Ligases, PARK2, PARK6, PINK1, Parkin, Parkinson’s disease, S-nitrosylation, mitophagy, Medical Physiology, Biological sciences
Abstract

Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases Parkin translocation to mitochondrial membranes, disrupting mitophagy in cell lines and human-iPSC-derived neurons. We find levels of SNO-PINK1 in brains of α-synuclein transgenic PD mice similar to those in cell-based models, indicating the pathophysiological relevance of our findings. Importantly, SNO-PINK1-mediated deficits in mitophagy contribute to neuronal cell death. These results reveal a direct molecular link between nitrosative stress, SNO-PINK1 formation, and mitophagic dysfunction that contributes to the pathogenesis of PD.

Published
2017

3. S-Nitrosylation-Mediated Redox Transcriptional Switch Modulates Neurogenesis and Neuronal Cell Death

Author

Okamoto, Shu-ichi, Nakamura, Tomohiro, Cieplak, Piotr, Chan, Shing Fai, Kalashnikova, Evgenia, Liao, Lujian, Saleem, Sofiyan, Han, Xuemei, Clemente, Arjay, Nutter, Anthony, Sances, Sam, Brechtel, Christopher, Haus, Daniel, Haun, Florian, Sanz-Blasco, Sara, Huang, Xiayu, Li, Hao, Zaremba, Jeffrey D, Cui, Jiankun, Gu, Zezong, Nikzad, Rana, Harrop, Anne, McKercher, Scott R, Godzik, Adam, Yates, John R, and Lipton, Stuart A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Genetics, Neurodegenerative, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Generic health relevance, Animals, Apoptosis, Binding Sites, Cells, Cultured, DNA, HEK293 Cells, Humans, MEF2 Transcription Factors, Mice, Neural Stem Cells, Neurogenesis, Nitric Oxide, Oxidation-Reduction, Protein Binding, Protein Processing, Post-Translational, Transcriptional Activation, Medical Physiology, Biological sciences
Abstract

Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here, we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade.

Published
2014

9. HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies

Author

Rantalainen, Kimmo, primary, Berndsen, Zachary T., additional, Antanasijevic, Aleksandar, additional, Schiffner, Torben, additional, Zhang, Xi, additional, Lee, Wen-Hsin, additional, Torres, Jonathan L., additional, Zhang, Lei, additional, Irimia, Adriana, additional, Copps, Jeffrey, additional, Zhou, Kenneth H., additional, Kwon, Young D., additional, Law, William H., additional, Schramm, Chaim A., additional, Verardi, Raffaello, additional, Krebs, Shelly J., additional, Kwong, Peter D., additional, Doria-Rose, Nicole A., additional, Wilson, Ian A., additional, Zwick, Michael B., additional, Yates, John R., additional, Schief, William R., additional, and Ward, Andrew B., additional

Published
2020
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10. Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks

Author

Stein, Benjamin D., primary, Calzolari, Diego, additional, Hellberg, Kristina, additional, Hu, Ying S., additional, He, Lin, additional, Hung, Chien-Min, additional, Toyama, Erin Q., additional, Ross, Debbie S., additional, Lillemeier, Björn F., additional, Cantley, Lewis C., additional, Yates, John R., additional, and Shaw, Reuben J., additional

Published
2019
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12. Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer’s Disease-like Pathology

Author

Savas, Jeffrey N., primary, Wang, Yi-Zhi, additional, DeNardo, Laura A., additional, Martinez-Bartolome, Salvador, additional, McClatchy, Daniel B., additional, Hark, Timothy J., additional, Shanks, Natalie F., additional, Cozzolino, Kira A., additional, Lavallée-Adam, Mathieu, additional, Smukowski, Samuel N., additional, Park, Sung Kyu, additional, Kelly, Jeffery W., additional, Koo, Edward H., additional, Nakagawa, Terunaga, additional, Masliah, Eliezer, additional, Ghosh, Anirvan, additional, and Yates, John R., additional

Published
2017
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13. Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

Author

Jin, Meiyan, primary, Fuller, Gregory G., additional, Han, Ting, additional, Yao, Yao, additional, Alessi, Amelia F., additional, Freeberg, Mallory A., additional, Roach, Nathan P., additional, Moresco, James J., additional, Karnovsky, Alla, additional, Baba, Misuzu, additional, Yates, John R., additional, Gitler, Aaron D., additional, Inoki, Ken, additional, Klionsky, Daniel J., additional, and Kim, John K., additional

Published
2017
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20. Unbiased Identification of transRegulators of ADAR and A-to-I RNA Editing

Author

Freund, Emily C., Sapiro, Anne L., Li, Qin, Linder, Sandra, Moresco, James J., Yates, John R., and Li, Jin Billy

Abstract

Adenosine-to-inosine RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes that deaminate adenosine to inosine. Although many RNA editing sites are known, few transregulators have been identified. We perform BioID followed by mass spectrometry to identify transregulators of ADAR1 and ADAR2 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. Using ENCODE data, we validate and characterize a subset of the novel interactors as global or site-specific RNA editing regulators. Our set of novel transregulators includes all four members of the DZF-domain-containing family of proteins: ILF3, ILF2, STRBP, and ZFR. We show that these proteins interact with each ADAR and modulate RNA editing levels. We find ILF3 is a broadly influential negative regulator of editing. This work demonstrates the broad roles that RNA binding proteins play in regulating editing levels, and establishes DZF-domain-containing proteins as a group of highly influential RNA editing regulators.

Published
2020
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21. Integrated In VivoQuantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function

Author

Wortham, Matthew, Benthuysen, Jacqueline R., Wallace, Martina, Savas, Jeffrey N., Mulas, Francesca, Divakaruni, Ajit S., Liu, Fenfen, Albert, Verena, Taylor, Brandon L., Sui, Yinghui, Saez, Enrique, Murphy, Anne N., Yates, John R., Metallo, Christian M., and Sander, Maike

Abstract

Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivoquantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from 1-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides an in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in β cell function.

Published
2018
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22. Arginylation of myosin heavy chain regulates skeletal muscle strength.

Author

Cornachione AS, Leite FS, Wang J, Leu NA, Kalganov A, Volgin D, Han X, Xu T, Cheng YS, Yates JR 3rd, Rassier DE, and Kashina A

Subjects
Actin Cytoskeleton metabolism, Aminoacyltransferases genetics, Animals, Mice, Muscle, Skeletal physiology, Aminoacyltransferases metabolism, Muscle Contraction, Muscle, Skeletal metabolism, Myofibrils metabolism, Myosin Heavy Chains metabolism, Protein Processing, Post-Translational
Abstract

Protein arginylation is a posttranslational modification with an emerging global role in the regulation of actin cytoskeleton. To test the role of arginylation in the skeletal muscle, we generated a mouse model with Ate1 deletion driven by the skeletal muscle-specific creatine kinase (Ckmm) promoter. Ckmm-Ate1 mice were viable and outwardly normal; however, their skeletal muscle strength was significantly reduced in comparison to controls. Mass spectrometry of isolated skeletal myofibrils showed a limited set of proteins, including myosin heavy chain, arginylated on specific sites. Atomic force microscopy measurements of contractile strength in individual myofibrils and isolated myosin filaments from these mice showed a significant reduction of contractile forces, which, in the case of myosin filaments, could be fully rescued by rearginylation with purified Ate1. Our results demonstrate that arginylation regulates force production in muscle and exerts a direct effect on muscle strength through arginylation of myosin., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2014
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