Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

Omairi, Saleh; Hau, Kwan Leong; Collins-Hooper, Henry; Scott, Charlotte; Vaiyapuri, Sakthivel; Torelli, Silvia; Montanaro, Federica; Matsakas, Antonios; Patel, Ketan

Abstract

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma. 2

Citation

Omairi, S., Hau, K. L., Collins-Hooper, H., Scott, C., Vaiyapuri, S., Torelli, S., Montanaro, F., Matsakas, A., & Patel, K. (2019). Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres. Scientific reports, 9(1), Article 2770. https://doi.org/10.1038/s41598-019-39532-4

• Journal Article Type: Article
• Acceptance Date: Jan 10, 2019
• Online Publication Date: Feb 26, 2019
• Publication Date: Dec 1, 2019
• Deposit Date: Feb 8, 2019
• Publicly Available Date: Mar 8, 2019
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 2770
• DOI: https://doi.org/10.1038/s41598-019-39532-4
• Keywords: Multidisciplinary
• Public URL: https://hull-repository.worktribe.com/output/1211004
• Publisher URL: https://www.nature.com/articles/s41598-019-39532-4
• Additional Information: Received: 29 December 2017; Accepted: 10 January 2019; First Online: 26 February 2019; : The authors declare no competing interests.
• Contract Date: Feb 8, 2019