title: Less is more: how protein degradation regulates muscle development.
abstract: The organization of sarcomeric structures during muscle development involves regulated multistep assembly pathways. The myosin assembly factor UNC-45 functions both as a molecular chaperone and as an Hsp90 co-chaperone for myosin throughout muscle thick-filament formation. Consequently, mutations in unc-45 result in paralyzed worms with severe myofibril disorganization in striated body wall muscles. Our data suggest that functional muscle formation in Caenorhabditis elegans is linked to ubiquitin-dependent UNC-45 turnover, regulated by the E3 enzymes UFD-2 and CHN-1 in cooperation with the ubiquitin-selective chaperone CDC-48 (also known as p97 in human). Missense mutations in the gene encoding p97 are known to cause a dominant, late-onset hereditary inclusion body myopathy. Remarkably, we identified a conserved role of CDC-48/p97 in the process of myofiber differentiation and maintenance, which appears to have important implications for understanding defects in muscle formation and maintenance during pathological conditions.
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases at the Institute for Genetics, University of Cologne, Zülpicher Str. 47, 50674 Cologne, Germany. thorsten.hoppe@zmnh.uni-hamburg.de
authors.forename: T
authors.initials: T
authors.lastname: Hoppe
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D024510:Muscle Development; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism
chemical_list: D009124:Muscle Proteins