Cardiac Myosin Light Chain-2. A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart
- Rottbauer, W., Wessels, G., Dahme, T., Just, S., Trano, N., Hassel, D., Burns, C.G., Katus, H.A., and Fishman, M.C.
- Circulation research 99(3): 323-331 (Journal)
- Registered Authors
- Burns, Geoff, Dahme, Tillmann, Fishman, Mark C., Hassel, David, Just, Steffen, Rottbauer, Wolfgang, Trano, Nicole, Wessels, Georgia
- cardiac myosin light chain-2, myofibrillogenesis, zebrafish heart
- MeSH Terms
- Cardiac Myosins/metabolism
- Cardiac Myosins/physiology*
- Embryo, Nonmammalian
- Heart/growth & development*
- Heart Atria/cytology
- Heart Ventricles/cytology
- Muscle Development*
- Myocardial Contraction*
- Myosin Light Chains/metabolism
- Myosin Light Chains/physiology*
- 16809551 Full text @ Circ. Res.
Rottbauer, W., Wessels, G., Dahme, T., Just, S., Trano, N., Hassel, D., Burns, C.G., Katus, H.A., and Fishman, M.C. (2006) Cardiac Myosin Light Chain-2. A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart. Circulation research. 99(3):323-331.
Although it is well known that mutations in the cardiac regulatory myosin light chain-2 (mlc-2) gene cause hypertrophic cardiomyopathy, the precise in vivo structural and functional roles of MLC-2 in the heart are only poorly understood. We have isolated a mutation in zebrafish, tell tale heart (tel(m225)), which selectively perturbs contractility of the embryonic heart. By positional cloning, we identified tel to encode the zebrafish mlc-2 gene. In contrast to mammals, zebrafish have only 1 cardiac-specific mlc-2 gene, which we find to be expressed in atrial and ventricular cardiomyocytes during early embryonic development, but also in the adult heart. Accordingly, loss of zMLC-2 function cannot be compensated for by upregulation of another mlc-2 gene. Surprisingly, ultrastructural analysis of tel cardiomyocytes reveals complete absence of organized thick myofilaments. Thus, our findings provide the first in vivo evidence that cardiac MLC-2 is required for thick-filament stabilization and contractility in the vertebrate heart.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes