How protein networks stabilise muscle fibres
Same mechanism known for DNA now found for muscle proteins
Research team with RUB involvement reports in Genes and Development
Methylation in the nucleus
Enzymes, called methyltransferases, transfer methyl (CH3) groups to specific sections of the DNA in the nucleus. In this way, they mark active and inactive regions of the genes. However, not only DNA but also nuclear proteins incur methylation, mostly at the amino acid lysine. Methylated lysines on nuclear proteins promote the formation of protein complexes that control, for example, DNA repair and replication. However, methyltransferases are not only found in the nucleus, but also in the cellular fluid (cytoplasm). Yet, it is not well established which proteins they methylate in the cytoplasm and how this methylation may affect function.
Shown for the first time: methylation in the cytoplasm promotes protein complex formation
The researchers first identified an enzyme which is mainly present in the cytoplasm and which methylates the amino acid lysine (Smyd2). Then they searched for interaction partners of the enzyme Smyd2 and found the heat shock protein Hsp90. The scientists went on to show that Smyd2 and methylated Hsp90 form a complex with the muscle protein titin. “Titin is the largest protein in the human body and known primarily for its role as an elastic spring in muscle cells” explains Linke. “Precisely this elastic region of titin is protected by the association with methylated Hsp90.”
Titin requires protection by methylated proteins
In skeletal muscle cells of the zebrafish, Linke’s team explored what happens when the protection by the methylated heat shock protein is repressed. By genetic manipulation they altered the organism in such a way that it no longer produced the enzyme Smyd2, which blocked the methylation of Hsp90. Without methylated Hsp90, the elastic titin region was unstable and muscle function strongly impaired; the regular muscle structure was partially disrupted.
Bibliographic record
L.T. Donlin, C. Andresen, S. Just, E. Rudensky, C.T. Pappas, M. Kruger, E.Y. Jacobs, A. Unger, A. Zieseniss, M.-W. Dobenecker, T. Voelkel, B.T. Chait, C.C. Gregorio, W. Rottbauer, A. Tarakhovsky, W.A. Linke (2012): Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization, Genes and Development, doi: 10.1101/gad.177758.111
