PUBLICATION
Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression
- Authors
- Eden, M., Meder, B., Völkers, M., Poomvanicha, M., Domes, K., Branchereau, M., Marck, P., Will, R., Bernt, A., Rangrez, A., Busch, M., German Mouse Clinic Consortium, Hrab? de Angelis, M., Heymes, C., Rottbauer, W., Most, P., Hofmann, F., Frey, N.
- ID
- ZDB-PUB-160429-11
- Date
- 2016
- Source
- Nature communications 7: 11317 (Journal)
- Registered Authors
- Meder, Benjamin
- Keywords
- Cell biology, Medical research
- MeSH Terms
-
- Animals
- Calcium/metabolism*
- Mice, Knockout
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism
- Gene Expression Regulation*
- Zebrafish/genetics
- Zebrafish/metabolism
- Humans
- Cells, Cultured
- Myocardium/metabolism*
- Animals, Newborn
- Myocardial Contraction/genetics
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/physiology
- HEK293 Cells
- Calcium Channels, L-Type/genetics*
- Calcium Channels, L-Type/metabolism
- Rats, Wistar
- Rats, Sprague-Dawley
- Mice, Inbred C57BL
- Protein Binding
- PubMed
- 27122098 Full text @ Nat. Commun.
Citation
Eden, M., Meder, B., Völkers, M., Poomvanicha, M., Domes, K., Branchereau, M., Marck, P., Will, R., Bernt, A., Rangrez, A., Busch, M., German Mouse Clinic Consortium, Hrab? de Angelis, M., Heymes, C., Rottbauer, W., Most, P., Hofmann, F., Frey, N. (2016) Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression. Nature communications. 7:11317.
Abstract
Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca(2+) transients and enhances L-type Ca(2+) channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca(2+)currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease.
Errata / Notes
This article is corrected by ZDB-PUB-220906-43.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping