title: Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin ligase, mysterin/RNF213.
abstract: Mysterin (also known as RNF213) is a huge intracellular protein with two AAA+ ATPase modules and a RING finger ubiquitin ligase domain. Mysterin was originally isolated as a significant risk factor for the cryptogenic cerebrovascular disorder moyamoya disease, and was found to be involved in physiological angiogenesis in zebrafish. However, the function and the physiological significance of mysterin in other than blood vessels remain largely unknown, although mysterin is ubiquitously expressed in animal tissues. In this study, we performed antisense-mediated suppression of a mysterin orthologue in zebrafish larvae and revealed that mysterin-deficient larvae showed significant reduction in fast myofibrils and immature projection of primary motoneurons, leading to severe motor deficits. Fast muscle-specific restoration of mysterin expression cancelled these phenotypes, and interestingly both AAA+ ATPase and ubiquitin ligase activities of mysterin were indispensable for proper fast muscle formation, demonstrating an essential role of mysterin and its enzymatic activities in the neuromuscular regulation in zebrafish.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 606-8397, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotani
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 606-8397, Japan.|Department of Medical Biochemistry, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morito
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center, Suita 565-8565, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University, Sagamihara 252-5258, Japan.|Center for Frontier Research, National Institute of Genetics, Mishima 411-8540, Japan.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Ogino
authors.affiliation: Division of Molecular and Developmental Biology, National Institute of Genetics and Department of Genetics, Sokendai (The Graduate University for Advanced Studies), Mishima 411-8540, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Chemistry and Biological Science, School of Science and Engineering, Aoyama Gakuin University, Sagamihara 252-5258, Japan.|Center for Frontier Research, National Institute of Genetics, Mishima 411-8540, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 606-8397, Japan.|CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007814:Larva / Q000378:metabolism; D008854:Microscopy, Electron; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D054829:RING Finger Domains; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; D044767:Ubiquitin-Protein Ligases