The giant protein titin regulates the length of the striated muscle thick filament

Paola Tonino, Balazs Kiss, Josh Strom, Mei Methawasin, John E. Smith, Justin Kolb, Siegfried Labeit, Hendrikus "Henk" Granzier

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1041
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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Connectin
skeletal muscle
Striated Muscle
muscles
Muscle
filaments
proteins
Muscles
Myocardium
Skeletal Muscle
Proteins
Dilated Cardiomyopathy
Myosins
myosins
phenotype
Phenotype
machinery
Health
health
Machinery

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

The giant protein titin regulates the length of the striated muscle thick filament. / Tonino, Paola; Kiss, Balazs; Strom, Josh; Methawasin, Mei; Smith, John E.; Kolb, Justin; Labeit, Siegfried; Granzier, Hendrikus "Henk".

In: Nature Communications, Vol. 8, No. 1, 1041, 01.12.2017.

Research output: Contribution to journalArticle

Tonino, P, Kiss, B, Strom, J, Methawasin, M, Smith, JE, Kolb, J, Labeit, S & Granzier, HH 2017, 'The giant protein titin regulates the length of the striated muscle thick filament', Nature Communications, vol. 8, no. 1, 1041. https://doi.org/10.1038/s41467-017-01144-9
Tonino, Paola ; Kiss, Balazs ; Strom, Josh ; Methawasin, Mei ; Smith, John E. ; Kolb, Justin ; Labeit, Siegfried ; Granzier, Hendrikus "Henk". / The giant protein titin regulates the length of the striated muscle thick filament. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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