title: Drosophila UNC-45 accumulates in embryonic blastoderm and in muscles, and is essential for muscle myosin stability.
abstract: UNC-45 is a chaperone that facilitates folding of myosin motor domains. We have used Drosophila melanogaster to investigate the role of UNC-45 in muscle development and function. Drosophila UNC-45 (dUNC-45) is expressed at all developmental stages. It colocalizes with non-muscle myosin in embryonic blastoderm of 2-hour-old embryos. At 14 hours, it accumulates most strongly in embryonic striated muscles, similarly to muscle myosin. dUNC-45 localizes to the Z-discs of sarcomeres in third instar larval body-wall muscles. We produced a dunc-45 mutant in which zygotic expression is disrupted. This results in nearly undetectable dUNC-45 levels in maturing embryos as well as late embryonic lethality. Muscle myosin accumulation is robust in dunc-45 mutant embryos at 14 hours. However, myosin is dramatically decreased in the body-wall muscles of 22-hour-old mutant embryos. Furthermore, electron microscopy showed only a few thick filaments and irregular thick-thin filament lattice spacing. The lethality, defective protein accumulation, and ultrastructural abnormalities are rescued with a wild-type dunc-45 transgene, indicating that the mutant phenotypes arise from the dUNC-45 deficiency. Overall, our data indicate that dUNC-45 is important for myosin accumulation and muscle function. Furthermore, our results suggest that dUNC-45 acts post-translationally for proper myosin folding and maturation.
authors.affiliation: Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Chi F
authors.initials: CF
authors.lastname: Lee
authors.forename: Girish C
authors.initials: GC
authors.lastname: Melkani
authors.forename: Qin
authors.initials: Q
authors.lastname: Yu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Suggs
authors.forename: William A
authors.initials: WA
authors.lastname: Kronert
authors.forename: Yoko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Lori
authors.initials: L
authors.lastname: Hipolito
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Price
authors.forename: Henry F
authors.initials: HF
authors.lastname: Epstein
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D001756:Blastoderm / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D009218:Myosins / Q000378:metabolism*; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D018832:Molecular Chaperones; C550552:UNC-45 protein, Drosophila; D009218:Myosins