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Molecular mechanism regulating myosin and cardiac functions by ELC

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Item Type:Article
Title:Molecular mechanism regulating myosin and cardiac functions by ELC
Creators Name:Lossie, J., Köhncke, C., Mahmoodzadeh, S., Steffen, W., Canepari, M., Maffei, M., Taube, M., Larchevêque, O., Baumert, P., Haase, H., Bottinelli, R., Regitz-Zagrosek, V. and Morano, I.
Abstract:The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. We therefore generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1; TgM(hVLC-1)) or E56G-mutated hVLC-1 (hVLC-1(E56G); TgM(E56G)). hVLC-1 or hVLC-1(E56G) expression in TgM was around 39% and 41%, respectively of total VLC-1. Laser trap and in vitro motility assays showed that stiffness and actin sliding velocity of myosin with hVLC-1 prepared from TgM(hVLC-1) (1.67pN/nm and 2.3{my}m/s, respectively) were significantly higher than myosin with hVLC-1(E56G) prepared from TgM(E56G) (1.25pN/nm and 1.7{my}m/s, respectively) or myosin with mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5+-0.03 {my}m/s, respectively). Maximal left ventricular pressure development of isolated perfused hearts in vitro prepared from TgM(hVLC-1) (80.0mmHg) were significantly higher than hearts from TgM(E56G) (66.2mmHg) or C57/BL6 (59.3+-3.9 mmHg). These findings show that ELCs decreased myosin stiffness, in vitro motility, and thereby cardiac functions in the order hVLC-1 > hVLC-1(E56G) ≈ mVLC-1. They also suggest a molecular pathomechanism of cardiomyopathies caused by hVLC-1 mutations.
Keywords:Essential Myosin Light Chains, Myosin, Stiffness, In Vitro Motility, Mutations, Animals, Mice
Source:Biochemical and Biophysical Research Communications
Publisher:Academic Press
Page Range:464-469
Date:18 July 2014
Official Publication:https://doi.org/10.1016/j.bbrc.2014.05.142
PubMed:View item in PubMed

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