PUBLICATION

Cardiac Myosin Light Chain-2. A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart

Authors
Rottbauer, W., Wessels, G., Dahme, T., Just, S., Trano, N., Hassel, D., Burns, C.G., Katus, H.A., and Fishman, M.C.
ID
ZDB-PUB-060703-19
Date
2006
Source
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
Keywords
cardiac myosin light chain-2, myofibrillogenesis, zebrafish heart
MeSH Terms
  • Animals
  • Cardiac Myosins/metabolism
  • Cardiac Myosins/physiology*
  • Embryo, Nonmammalian
  • Heart/embryology
  • Heart/growth & development*
  • Heart/physiology*
  • Heart Atria/cytology
  • Heart Ventricles/cytology
  • Muscle Development*
  • Mutation
  • Myocardial Contraction*
  • Myosin Light Chains/metabolism
  • Myosin Light Chains/physiology*
  • Phosphorylation
  • Zebrafish
PubMed
16809551 Full text @ Circ. Res.
Abstract
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
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Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes