Escape from the nucleus: The role of cytoplasmic protein methylation

Protein complexes in a muscle cell. Image provided by RUB. © Prof. Wolfgang A. Linke

Alexander Tarakhovsky and colleagues from The Rockefeller University along with colleagues from Ruhr-University Bochum (Germany) have shown that protein methylation in the cytoplasm promotes protein complex formation.

While we are all familiar with the role of methyltransferase in DNA and protein modification in the nucleus, (think epigenetics with regards to DNA), this is the first time that methylation in the cytoplasm has been shown to promote 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.

According to the authors, “Titin is the largest protein in the human body and known primarily for its role as an elastic spring in muscle cells. Precisely this elastic region of titin is protected by the association with methylated Hsp90.”

In skeletal muscle cells of the zebrafish, the 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.

Click here for a link to the Genes and Development paper.

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