Reduced passive force in skeletal muscles lacking protein arginylation

Felipe S. Leite, Fábio C. Minozzo, Albert Kalganov, Anabelle S. Cornachione, Yu Shu Cheng, Nicolae A. Leu, Xuemei Han, Chandra Saripalli, John R. Yates, Henk Granzier, Anna S. Kashina, Dilson E. Rassier

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Arginy-lation is a posttranslational modification that plays a global role in mammals. Mice lacking the enzyme arginyltransferase in skeletal muscles exhibit reduced contractile forces that have been linked to a reduction in myosin cross-bridge formation. The role of arginylation in passive skeletal myofibril forces has never been investigated. In this study, we used single sarcomere and myofibril measurements and observed that lack of arginylation leads to a pronounced reduction in passive forces in skeletal muscles. Mass spectrometry indicated that skeletal muscle titin, the protein primarily linked to passive force generation, is arginylated on five sites located within the A band, an important area for protein-protein interactions. We propose a mech- anism for passive force regulation by arginylation through modulation of protein-protein binding between the titin molecule and the thick filament. Key points are as follows: 1) active and passive forces were decreased in myofibrils and single sarcomeres isolated from muscles lacking arginyl-tRNA-protein transferase (ATE1). 2) Mass spectrom- etry revealed five sites for arginylation within titin molecules. All sites are located within the A-band portion of titin, an important region for protein-protein interactions. 3) Our data suggest that arginylation of titin is required for proper passive force development in skeletal muscles.

Original languageEnglish (US)
Pages (from-to)C127-C135
JournalAmerican Journal of Physiology - Cell Physiology
Volume310
Issue number2
DOIs
StatePublished - Jan 15 2016

Keywords

  • Arginylation
  • Myofibril
  • Passive force
  • Posttranslational modification
  • Sarcomere
  • Titin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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  • Cite this

    Leite, F. S., Minozzo, F. C., Kalganov, A., Cornachione, A. S., Cheng, Y. S., Leu, N. A., Han, X., Saripalli, C., Yates, J. R., Granzier, H., Kashina, A. S., & Rassier, D. E. (2016). Reduced passive force in skeletal muscles lacking protein arginylation. American Journal of Physiology - Cell Physiology, 310(2), C127-C135. https://doi.org/10.1152/ajpcell.00269.2015