Regulation of the Myosin-Directed Chaperone UNC-45 by a Novel E3/E4-Multiubiquitylation Complex in C. elegans

• Published in: Cell Vol. 118; no. 3; pp. 337 - 349
• Main Authors: Hoppe, Thorsten, Cassata, Giuseppe, Barral, José M., Springer, Wolfdieter, Hutagalung, Alex H., Epstein, Henry F., Baumeister, Ralf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.08.2004
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Mutation; Myosins - metabolism; Temperature; Ubiquitin-Conjugating Enzymes - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2004.07.014

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.