The giant protein titin regulates the length of the striated muscle thick filament
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Author
Tonino, PaolaKiss, Balazs
Strom, Josh
Methawasin, Mei
Smith, John E.

Kolb, Justin
Labeit, Siegfried
Granzier, Henk
Affiliation
Univ Arizona, Dept Cellular & Mol MedUniv Arizona, Sarver Mol Cardiovasc Res Program
Issue Date
2017-10-19
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NATURE PUBLISHING GROUPCitation
The giant protein titin regulates the length of the striated muscle thick filament 2017, 8 (1) Nature CommunicationsJournal
Nature CommunicationsRights
© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin's C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.ISSN
2041-1723PubMed ID
29051486Version
Final published versionSponsors
Foundation Leducq [TNE-13CVD04]; National Institutes of Health [HL062881, HL118524, HL115988]Additional Links
http://www.nature.com/articles/s41467-017-01144-9ae974a485f413a2113503eed53cd6c53
10.1038/s41467-017-01144-9
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Except where otherwise noted, this item's license is described as © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.
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