title: Protective role of cell division cycle 48 (CDC48) protein against neurodegeneration via ubiquitin-proteasome system dysfunction during zebrafish development.
abstract: Cell division cycle 48 (CDC48), a ubiquitin-dependent molecular chaperone, is thought to mediate a variety of degradative and regulatory processes and maintain cellular homoeostasis. To investigate the protective function of CDC48 against accumulated ubiquitinated proteins during neurodevelopment, we developed an in vivo bioassay technique that detects expression and accumulation of fluorescent proteins with a polyubiquitination signal at the N terminus. When we introduced CDC48 antisense morpholino oligonucleotides into zebrafish embryos, the morphant embryos were lethal and showed defects in neuronal outgrowth and neurodegeneration, and polyubiquitinated fluorescent proteins accumulated in the inner plexiform and ganglion cell layers, as well as the diencephalon and mesencephalon, indicating that the degradation of polyubiquitinated proteins by the ubiquitin-proteasome system was blocked. These abnormal phenotypes in the morphant were rescued by CDC48 or human valosin-containing protein overexpression. Therefore, the protective function of CDC48 is essential for neurodevelopment.
authors.affiliation: National Research Institute of Fisheries Science, 2-12-4 Fukuura, Yokohama, Kanagawa 236-8648, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Imamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yabu
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamashita
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004027:Diencephalon / Q000002:abnormalities / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008636:Mesencephalon / Q000002:abnormalities / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000201:enzymology; D013116:Spinal Cord / Q000002:abnormalities / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein