Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans

Thorsten Hoppe, Giuseppe Cassata, José M. Barral, Wolfdieter Springer, Alex H. Hutagalung, Henry F. Epstein, Ralf Baumeister

    Research output: Contribution to journalArticlepeer-review

    105 Scopus citations

    Abstract

    The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.

    Original languageEnglish (US)
    Pages (from-to)337-349
    Number of pages13
    JournalCell
    Volume118
    Issue number3
    DOIs
    StatePublished - Aug 6 2004

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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