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An Extensive Atlas of Proteome and Phosphoproteome Turnover Across Mouse Tissues and Brain Regions

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机构: [1]Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. [2]Cancer Biology Institute, Yale University School of Medicine, West Haven, CT 06516, USA. [3]Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. [4]Department of Pulmonary and Critical Care Medicine, and Proteomics-Metabolomics Analysis Platform, West China Hospital, Sichuan University, Chengdu 610041, China. [5]Department of Neuro- and Sensory Physiology, University Medical Center Gottingen, 37073 Gottingen, Germany. [6]Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. [7]Current address: Department of Computer Science and Engineering, SRM University AP, Neerukonda, Guntur, Andhra Pradesh 522240, India. [8]Current address: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. [9]Current address: Interdisciplinary Research center on Biology and chemistry, Shanghai institute of Organic chemistry, Chinese Academy of Sciences, Shanghai 201210, China. [10]Department of Biomedical Informatics & Data Science, Yale University School of Medicine, New Haven, CT 06510, USA.
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Understanding how proteins in different mammalian tissues are regulated is central to biology. Protein abundance, turnover, and post-translational modifications like phosphorylation, are key factors that determine tissue-specific proteome properties. However, these properties are challenging to study across tissues and remain poorly understood. Here, we present Turnover-PPT, a comprehensive resource mapping the abundance and lifetime of 11,000 proteins and 40,000 phosphosites across eight mouse tissues and various brain regions, using advanced proteomics and stable isotope labeling. We revealed tissue-specific short- and long-lived proteins, strong correlations between interacting protein lifetimes, and distinct impacts of phosphorylation on protein turnover. Notably, we discovered that peroxisomes are regulated by protein turnover across tissues, and that phosphorylation regulates the stability of neurodegeneration-related proteins, such as Tau and α-synuclein. Thus, Turnover-PPT provides new fundamental insights into protein stability, tissue dynamic proteotypes, and the role of protein phosphorylation, and is accessible via an interactive web-based portal at https://yslproteomics.shinyapps.io/tissuePPT.

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第一作者机构: [1]Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. [2]Cancer Biology Institute, Yale University School of Medicine, West Haven, CT 06516, USA.
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通讯机构: [1]Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. [2]Cancer Biology Institute, Yale University School of Medicine, West Haven, CT 06516, USA. [5]Department of Neuro- and Sensory Physiology, University Medical Center Gottingen, 37073 Gottingen, Germany. [6]Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. [10]Department of Biomedical Informatics & Data Science, Yale University School of Medicine, New Haven, CT 06510, USA.
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