title: Analysis of the two p97/VCP/Cdc48p proteins of Caenorhabditis elegans and their suppression of polyglutamine-induced protein aggregation.
abstract: A class of inherited neurodegenerative diseases including Huntington's disease is caused by polyglutamine (polyQ) expansion in the responsible proteins. Pathology is typically associated with polyQ expansions of greater than 40 residues, and the longer the length of the expansion, the earlier the onset of disease. It has been reported that p97/VCP/Cdc48p, a member of AAA family of proteins, can bind to longer polyQ tracts. In Caenorhabditis elegans, two p97/VCP/Cdc48p homologues, C41C4.8 and C06A1.1, have been identified. Our results indicate that these p97/VCP/Cdc48p homologues have essential but redundant functions in C. elegans. To provide a model system for investigating the molecular basis of pathogenesis, we have expressed polyQ expansions fused to green fluorescent protein in the body wall muscle cells of C. elegans. When the repeats are longer than 40, discrete cytoplasmic aggregates are formed and these appear at an early stage of embryogenesis. The formation of aggregates was partially suppressed by co-expression of either C41C4.8 or C06A1.1. These results suggest that these p97/VCP/Cdc48p homologues, AAA chaperones, may play a protective role in polyQ aggregation.
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan. yamanaka@gpo.kumamoto-u.ac.jp
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Okubo
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Suzaki
authors.forename: Teru
authors.initials: T
authors.lastname: Ogura
mesh_terms: D000251:Adenosine Triphosphatases; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000032:analysis* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000502:physiology*; D019281:Dimerization; D004625:Embryo, Nonmammalian; D008856:Microscopy, Fluorescence; D032342:Muscle Cells / Q000737:chemistry; D030781:Organisms, Genetically Modified; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014018:Tissue Distribution; D000074405:Valosin Containing Protein
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D010455:Peptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; C097188:polyglutamine; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein