Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization
Donlin, L.T., Andresen, C., Just, S., Rudensky, E., Pappas, C.T., Kruger, M., Jacobs, E.Y., Unger, A., Zieseniss, A., Dobenecker, M.W., Voelkel, T., Chait, B.T., Gregorio, C.C., Rottbauer, W., Tarakhovsky, A., and Linke, W.A.
Protein lysine methylation is one of the most widespread post-translational modifications in the nuclei of eukaryotic cells.
Methylated lysines on histones and nonhistone proteins promote the formation of protein complexes that control gene expression
and DNA replication and repair. In the cytoplasm, however, the role of lysine methylation in protein complex formation is
not well established. Here we report that the cytoplasmic protein chaperone Hsp90 is methylated by the lysine methyltransferase
Smyd2 in various cell types. In muscle, Hsp90 methylation contributes to the formation of a protein complex containing Smyd2,
Hsp90, and the sarcomeric protein titin. Deficiency in Smyd2 results in the loss of Hsp90 methylation, impaired titin stability,
and altered muscle function. Collectively, our data reveal a cytoplasmic protein network that employs lysine methylation for
the maintenance and function of skeletal muscle.