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

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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