The UNC-45 Chaperone Mediates Sarcomere Assembly Through Myosin Degradation in Caenorhabditis Elegans

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2007 Apr 18

PMID 17438072

Citations 65

Authors

Megan L Landsverk

Shumin Li

Alex H Hutagalung

Ayaz Najafov

Thorsten Hoppe

Jose M Barral

Henry F Epstein

Affiliations

Soon will be listed here.

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.

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