title: Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization.
abstract: 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.
authors.affiliation: Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Donlin
authors.forename: Christian
authors.initials: C
authors.lastname: Andresen
authors.forename: Steffen
authors.initials: S
authors.lastname: Just
authors.forename: Eugene
authors.initials: E
authors.lastname: Rudensky
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Pappas
authors.forename: Martina
authors.initials: M
authors.lastname: Kruger
authors.forename: Erica Y
authors.initials: EY
authors.lastname: Jacobs
authors.forename: Andreas
authors.initials: A
authors.lastname: Unger
authors.forename: Anke
authors.initials: A
authors.lastname: Zieseniss
authors.forename: Marc-Werner
authors.initials: MW
authors.lastname: Dobenecker
authors.forename: Tobias
authors.initials: T
authors.lastname: Voelkel
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: Carol C
authors.initials: CC
authors.lastname: Gregorio
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Linke
mesh_terms: D000818:Animals; D002642:Chick Embryo; D064211:Connectin; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D064211:Connectin; D018841:HSP90 Heat-Shock Proteins; D009124:Muscle Proteins; D011994:Recombinant Proteins; C577285:TTN protein, human; D011495:Histone-Lysine N-Methyltransferase; D011494:Protein Kinases; D008239:Lysine