| A single serine in the carboxyl terminus of cardiac essential myosin light chain-1 controls cardiomyocyte contractility in vivo. | |
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MedLine Citation:
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PMID: 19168438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although it is well known that mutations in the cardiac essential myosin light chain-1 (cmlc-1) gene can cause hypertrophic cardiomyopathy, the precise in vivo structural and functional roles of cMLC-1 in the heart are only poorly understood. We have isolated the zebrafish mutant lazy susan (laz), which displays severely reduced contractility of both heart chambers. By positional cloning, we identified a nonsense mutation within the zebrafish cmlc-1 gene to be responsible for the laz phenotype, leading to expression of a carboxyl-terminally truncated cMLC-1. Whereas complete loss of cMLC-1 leads to cardiac acontractility attributable to impaired cardiac sarcomerogenesis, expression of a carboxyl-terminally truncated cMLC-1 in laz mutant hearts is sufficient for normal cardiac sarcomerogenesis but severely impairs cardiac contractility in a cell-autonomous fashion. Whereas overexpression of wild-type cMLC-1 restores contractility of laz mutant cardiomyocytes, overexpression of phosphorylation site serine 195-deficient cMLC-1 (cMLC-1(S195A)) does not reconstitute cardiac contractility in laz mutant cardiomyocytes. By contrast, introduction of a phosphomimetic amino acid on position 195 (cMLC-1(S195D)) rescues cardiomyocyte contractility, demonstrating for the first time an essential role of the carboxyl terminus and especially of serine 195 of cMLC-1 in the regulation of cardiac contractility. |
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Authors:
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Benjamin Meder; Christina Laufer; David Hassel; Steffen Just; Sabine Marquart; Britta Vogel; Alexander Hess; Mark C Fishman; Hugo A Katus; Wolfgang Rottbauer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-22 |
Journal Detail:
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Title: Circulation research Volume: 104 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-03-16 Completed Date: 2009-04-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 650-9 Citation Subset: IM |
Affiliation:
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Department of Medicine III, University of Heidelberg, Heidelberg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Cloning, Molecular Codon, Nonsense Ethylnitrosourea / toxicity Gene Expression Regulation, Developmental Genotype Heart / drug effects, embryology* Models, Molecular Molecular Conformation Molecular Sequence Data Muscle Strength Mutagens / toxicity Myocardial Contraction* / genetics Myocytes, Cardiac / drug effects, metabolism* Myosin Light Chains / chemistry, genetics, metabolism* Phenotype Phosphorylation Protein Stability Protein Structure, Tertiary Sarcomeres / metabolism Sequence Homology, Amino Acid Serine Time Factors Zebrafish Zebrafish Proteins / chemistry, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cmlc1 protein, zebrafish; 0/Codon, Nonsense; 0/Mutagens; 0/Myosin Light Chains; 0/Zebrafish Proteins; 56-45-1/Serine; 759-73-9/Ethylnitrosourea |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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