Key result
Ate1 deletion reduces skeletal muscle contractile forces in mice, fully rescued by rearginylation.
Arginylation of myosin heavy chain by Ate1 is essential for normal force production and skeletal muscle strength.
Arginylation may support skeletal muscle strength; leaves open its role in human myopathies or therapeutic targeting.
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.
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Cornachione et al. (2014) studied Skeletal muscle strength. Ate1 deletion vs. Controls was evaluated on Skeletal muscle strength and contractile forces. Ate1 deletion in skeletal muscle significantly reduced contractile forces in individual myofibrils and isolated myosin filaments, which was fully rescued by rearginylation with purified Ate1.
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