Lysine methyltransferase Smyd2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function
2013 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Lysine methyltransferase Smyd2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function
Voelkel, T.; Andresen, C.; Unger, A.; Just, S.; Rottbauer, W. & Linke, W. A. (2013)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1833(4) pp. 812-822. DOI: https://doi.org/10.1016/j.bbamcr.2012.09.012
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- Authors
- Voelkel, Tobias; Andresen, Christian; Unger, Andreas; Just, Steffen; Rottbauer, Wolfgang; Linke, Wolfgang A.
- Abstract
- Protein lysine methylation controls gene expression and repair of deoxyribonucleic acid in the nucleus but also occurs in the cytoplasm, where the role of this posttranslational modification is less understood. Members of the Smyd protein family of lysine methyltransferases are particularly abundant in the cytoplasm, with Smyd1 and Smyd2 being most highly expressed in the heart and in skeletal muscles. Smyd1 is a crucial myogenic regulator with histone methyltransferase activity but also associates with myosin, which promotes sarcomere assembly. Smyd2 methylates histones and non-histone proteins, such as the tumor suppressors, p53 and retinoblastoma protein, RB. Smyd2 has an intriguing function in the cytoplasm of skeletal myocytes, where it methylates the chaperone Hsp90, thus promoting the interaction of a Smyd2-methyl-Hsp90 complex with the N2A-domain of titin. This complex protects the sarcomeric I-band region and myocyte organization. We briefly summarize some novel functions of Smyd family members, with a focus on Smyd2, and highlight their role in striated muscles and cytoplasmic actions. We then provide experimental evidence that Smyd2 is also important for cardiac function. In the cytoplasm of cardiomyocytes, Smyd2 was found to associate with the sarcomeric I-band region at the titin N2A-domain. Binding to N2A occurred in vitro and in yeast via N-terminal and extreme C-terminal regions of Smyd2. Smyd2-knockdown in zebrafish using an antisense oligonucleotide morpholino approach strongly impaired cardiac performance. We conclude that Smyd2 and presumably several other Smyd family members are lysine methyltransferases which have, next to their nuclear activity, specific regulatory functions in the cytoplasm of heart and skeletal muscle cells. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction. (C) 2012 Elsevier B.V. All rights reserved.
- Issue Date
- 2013
- Journal
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie - Working Group
- RG Linke (Kardiovaskuläre Physiologie)
- ISSN
- 0167-4889
- Sponsor
- European Union (MEDIA); German Research Foundation [SFB1002, TPB3]