The Role of the N-Terminus of the Myosin Essential Light Chain in Cardiac Muscle Contraction

Katarzyna Kazmierczak, Yuanyuan Xu, Michelle Jones, Georgianna Guzman, Olga M. Hernandez, W. Glenn L. Kerrick, Danuta Szczesna-Cordary

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice by partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43-amino-acid N-terminal truncation mutant (Tg-Δ43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle, and the ELC protein distribution in Tg-Δ43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Δ43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force-generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Δ43 mice and the mutant hearts develop a phenotype of nonpathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Δ43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin.

Original languageEnglish (US)
Pages (from-to)706-725
Number of pages20
JournalJournal of molecular biology
Volume387
Issue number3
DOIs
StatePublished - Apr 3 2009

Keywords

  • ATPase
  • cardiac myosin ELC
  • force in skinned papillary muscles
  • MRI
  • transgenic mice

ASJC Scopus subject areas

  • Molecular Biology

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