Rottbauer, Wolfgang;
Wessels, Georgia;
Dahme, Tillman;
Just, Steffen;
Trano, Nicole;
Hassel, David;
Burns, Charles Geoffrey;
Katus, Hugo A.;
Fishman, Mark C.
Cardiac Myosin Light Chain-2 : A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart
: A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart
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Medientyp:
E-Artikel
Titel:
Cardiac Myosin Light Chain-2 : A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart
:
A Novel Essential Component of Thick-Myofilament Assembly and Contractility of the Heart
Beteiligte:
Rottbauer, Wolfgang;
Wessels, Georgia;
Dahme, Tillman;
Just, Steffen;
Trano, Nicole;
Hassel, David;
Burns, Charles Geoffrey;
Katus, Hugo A.;
Fishman, Mark C.
Beschreibung:
<jats:p>
Although it is well known that mutations in the cardiac regulatory myosin light chain-2 (
<jats:italic>mlc-2</jats:italic>
) 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 (
<jats:italic>tel</jats:italic>
<jats:sup>m225</jats:sup>
), which selectively perturbs contractility of the embryonic heart. By positional cloning, we identified
<jats:italic>tel</jats:italic>
to encode the zebrafish
<jats:italic>mlc-2</jats:italic>
gene. In contrast to mammals, zebrafish have only 1 cardiac-specific
<jats:italic>mlc-2</jats:italic>
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
<jats:italic>mlc-2</jats:italic>
gene. Surprisingly, ultrastructural analysis of
<jats:italic>tel</jats:italic>
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.
</jats:p>