The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans.
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.
Landsverk
Megan L
ML
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Li
Shumin
S
Hutagalung
Alex H
AH
Najafov
Ayaz
A
Hoppe
Thorsten
T
Barral
José M
JM
Epstein
Henry F
HF
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018832:Molecular Chaperones; D025801:Ubiquitin; C107348:unc-45 protein, C elegans; D046988:Proteasome Endopeptidase Complex; D009218:Myosins