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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Reduced passive force in skeletal muscles lacking protein arginylation

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Author(s):
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Leite, Felipe S. [1] ; Minozzo, Fabio C. [1] ; Kalganov, Albert [1] ; Cornachione, Anabelle S. [1] ; Cheng, Yu-Shu [1] ; Leu, Nicolae A. [2] ; Han, Xuemei [3] ; Saripalli, Chandra [4] ; Yates, III, John R. ; Granzier, Henk [4] ; Kashina, Anna S. [2] ; Rassier, Dilson E. [1, 5]
Total Authors: 12
Affiliation:
[1] McGill Univ, Dept Kinesiol & Phys Educ, Montreal, PQ - Canada
[2] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 - USA
[3] III, Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 - USA
[4] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ - USA
[5] McGill Univ, Dept Phys & Physiol, Montreal, PQ - Canada
Total Affiliations: 5
Document type: Journal article
Source: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 310, n. 2, p. C127-C135, JAN 15 2016.
Web of Science Citations: 10
Abstract

Arginylation 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 mechanism 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 spectrometry 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. (AU)

FAPESP's process: 13/07104-6 - Effects of eccentric exercise in skeletal muscle rehabilitation of mdx mice after long period of training: morphological, functional and molecular evaluations
Grantee:Anabelle Silva Cornachione
Support type: Research Grants - Young Investigators Grants