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    Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype

    Murphy, Sandra and Zweyer, Margit and Raucamp, Maren and Henry, Michael and Meleady, Paula and Swandulla, Dieter and Ohlendieck, Kay (2019) Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype. Journal of Muscle Research and Cell Motility, 40. pp. 9-28. ISSN 0142-4319

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    The diaphragm is a crucial muscle involved in active inspiration and whole body homeostasis. Previous biochemical, immunochemical and cell biological investigations have established the distribution and fibre type-specific expression of key diaphragm proteins. Building on these findings, it was of interest to establish the entire experimentally assessable diaphragm proteome and verify the presence of specific protein isoforms within this specialized subtype of skeletal muscle. A highly sensitive Orbitrap Fusion Tribrid mass spectrometer was used for the systematic identification of the mouse diaphragmassociated protein population. Proteomics established 2925 proteins by high confidence peptide identification. Bioinformatics was used to determine the distribution of the main protein classes, biological processes and subcellular localization within the diaphragm proteome. Following the establishment of the respiratory muscle proteome with special emphasis on protein isoform expression in the contractile apparatus, the extra-sarcomeric cytoskeleton, the extracellular matrix and the excitation–contraction coupling apparatus, the mass spectrometric analysis of the diaphragm was extended to the refined identification of proteome-wide changes in X-linked muscular dystrophy. The comparative mass spectrometric profiling of the dystrophin-deficient diaphragm from the mdx-4cv mouse model of Duchenne muscular dystrophy identified 289 decreased and 468 increased protein species. Bioinformatics was employed to analyse the clustering of changes in protein classes and potential alterations in interaction patterns of proteins involved in metabolism, the contractile apparatus, proteostasis and the extracellular matrix. The detailed pathoproteomic profiling of the mdx-4cv diaphragm suggests highly complex alterations in a variety of crucial cellular processes due to deficiency in the membrane cytoskeletal protein dystrophin.

    Item Type: Article
    Additional Information: Funding: Research was supported by project grants from Muscular Dystrophy Ireland and the Irish Health Research Board (HRB/MRCG-2016-20) and a Hume scholarship from Maynooth University. The Orbitrap Fusion Tribrid mass spectrometer was funded under a Science Foundation Ireland Infrastructure Award to Dublin City University (SFI 16/RI/3701). Cite as: Murphy, S., Zweyer, M., Raucamp, M. et al. Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype. J Muscle Res Cell Motil 40, 9–28 (2019).
    Keywords: Diaphragm; Duchenne muscular dystrophy; Dystrophin; Dystrophinopathy; Mdx-4cv mouse; Skeletal muscle proteome;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 14162
    Identification Number:
    Depositing User: Prof. Kay Ohlendieck
    Date Deposited: 11 Mar 2021 14:41
    Journal or Publication Title: Journal of Muscle Research and Cell Motility
    Publisher: Springer
    Refereed: Yes
    Funders: Muscular Dystrophy Ireland, Health Research Board (HRB), Hume Scholarship (Maynooth University), Science Foundation Ireland (SFI)
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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