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Cell Rep. 2014 Jul 24;8(2):470-6. doi: 10.1016/j.celrep.2014.06.019. Epub 2014 Jul 10.

Arginylation of myosin heavy chain regulates skeletal muscle strength.

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  • 1Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
  • 2Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
  • 3The Scripps Research Institute, La Jolla, CA 92037, USA.
  • 4Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA. Electronic address: akashina@vet.upenn.edu.

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.

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