The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cell.2004.07.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans.
Nat Commun
August 2024
Institute for Genetics, University of Cologne, Cologne, Germany.
Mechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces.
View Article and Find Full Text PDFUNC-45 assisted myosin folding depends on a conserved FXHY motif implicated in Freeman Sheldon Syndrome.
Nat Commun
July 2024
Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.
Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control.
View Article and Find Full Text PDFThe myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.
Mol Biol Cell
July 2024
Department of Pathology, Emory University, Atlanta, GA 30322.
undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads.
View Article and Find Full Text PDFA ubiquitin fusion reporter to monitor muscle proteostasis in .
MicroPubl Biol
April 2023
Institute for Genetics, University of Cologne, Cologne, Germany.
Muscle is a highly dynamic tissue in which a variety of folding and degradation processes are active to maintain protein homeostasis (proteostasis) and functionality. The muscle-specific chaperone UNC-45 folds the motor protein myosin and assembles it into myofilaments. Malfunction of this chaperone leads to misfolding of myosin, disorganization of myofilaments, and degradation of misfolded myosin molecules by the proteasome.
View Article and Find Full Text PDFBeyond Chaperoning: UCS Proteins Emerge as Regulators of Myosin-Mediated Cellular Processes.
Subcell Biochem
December 2022
Department of Neuroscience, Cell Biology, & Anatomy, The University of Texas Medical Branch, Galveston, TX, USA.
The UCS (UNC-45/CRO1/She4p) family of proteins has emerged as chaperones specific for the folding, assembly, and function of myosin. UCS proteins participate in various myosin-dependent cellular processes including myofibril organization and muscle functions, cell differentiation, striated muscle development, cytokinesis, and endocytosis. Mutations in the genes that code for UCS proteins cause serious defects in myosin-dependent cellular processes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!