title: Arginylation of myosin heavy chain regulates skeletal muscle strength.
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.
authors.affiliation: Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Anabelle S
authors.initials: AS
authors.lastname: Cornachione
authors.affiliation: Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Felipe S
authors.initials: FS
authors.lastname: Leite
authors.affiliation: Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
authors.forename: Nicolae A
authors.initials: NA
authors.lastname: Leu
authors.affiliation: Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Kalganov
authors.affiliation: Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
authors.forename: Denys
authors.initials: D
authors.lastname: Volgin
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Han
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Kinesiology and Physical Education, Physics and Physiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Dilson E
authors.initials: DE
authors.lastname: Rassier
authors.affiliation: Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA. Electronic address: akashina@vet.upenn.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Kashina
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051379:Mice; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009210:Myofibrils / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D019881:Aminoacyltransferases; C019727:arginyltransferase; D018995:Myosin Heavy Chains