First Author | Kazmierczak K | Year | 2009 |
Journal | J Mol Biol | Volume | 387 |
Issue | 3 | Pages | 706-25 |
PubMed ID | 19361417 | Mgi Jnum | J:195614 |
Mgi Id | MGI:5484861 | Doi | 10.1016/j.jmb.2009.02.006 |
Citation | Kazmierczak K, et al. (2009) The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction. J Mol Biol 387(3):706-25 |
abstractText | 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-Delta43) 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-Delta43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Delta43 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-Delta43 mice and the mutant hearts develop a phenotype of nonpathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Delta43 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. |