The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans

Megan L. Landsverk, Shumin Li, Alex H. Hutagalung, Ayaz Najafov, Thorsten Hoppe, José M. Barral, Henry F. Epstein

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    Abstract

    Myosin motors are central to diverse cellular processes in eukaryotes. Homologues of the myosin chaperone UNC-45 have been implicated in the assembly and function of myosin-containing structures in organisms from fungi to humans. In muscle, the assembly of sarcomeric myosin is regulated to produce stable, uniform thick filaments. Loss-of-function mutations in Caenorhabditis elegans UNC-45 lead to decreased muscle myosin accumulation and defective thick filament assembly, resulting in paralyzed animals. We report that transgenic worms overexpressing UNC-45 also display defects in myosin assembly, with decreased myosin content and a mild paralysis phenotype. We find that the reduced myosin accumulation is the result of degradation through the ubiquitin/proteasome system. Partial proteasome inhibition is able to restore myosin protein and worm motility to nearly wild-type levels. These findings suggest a mechanism in which UNC-45-related proteins may contribute to the degradation of myosin in conditions such as heart failure and muscle wasting.

    Original languageEnglish (US)
    Pages (from-to)205-210
    Number of pages6
    JournalJournal of Cell Biology
    Volume177
    Issue number2
    DOIs
    StatePublished - Apr 23 2007

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    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Landsverk, M. L., Li, S., Hutagalung, A. H., Najafov, A., Hoppe, T., Barral, J. M., & Epstein, H. F. (2007). The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans. Journal of Cell Biology, 177(2), 205-210. https://doi.org/10.1083/jcb.200607084