Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization |
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| Authors: | Kyoko Kubota Natsuko Kumamoto Shinsuke Matsuzaki Ryota Hashimoto Tsuyoshi Hattori Hiroaki Okuda Hironori Takamura Masatoshi Takeda Taiichi Katayama Masaya Tohyama |
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| Institution: | 1. Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Chuo-ku, Niigata 951-8510, Japan;2. Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan;3. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan;4. Seiwa Hospital, Institute of Neuropsychiatry, 91 Bentencho, Shinjuku-ku, Tokyo 162-0851, Japan;5. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan;6. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan;7. Schizophrenia and Depression Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan;8. Laboratory of Health Education, Graduate School of Education, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;9. Department of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan;10. Molecular Research Center for Children''s Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, D3, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan;11. Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan;1. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA;2. Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA;3. National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA;4. NIH Intramural Sequencing Center, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA;5. Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA;6. NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892, USA;1. UPMC Univ Paris 06, CNRS-FRE 3402, 75252 Paris cedex 5, France;2. Department of Biology and the Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA |
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| Abstract: | A number of reports have provided genetic evidence for an association between the DTNBP1 gene (coding dysbindin) and schizophrenia. In addition, sandy mice, which harbor a deletion in the DTNBP1 gene and lack dysbindin, display behavioral abnormalities suggestive of an association with schizophrenia. However, the mechanism by which the loss of dysbindin induces schizophrenia-like behaviors remains unclear. Here, we report that small interfering RNA-mediated knockdown of dysbindin resulted in the aberrant organization of actin cytoskeleton in SH-SY5Y cells. Furthermore, we show that morphological abnormalities of the actin cytoskeleton were similarly observed in growth cones of cultured hippocampal neurons derived from sandy mice. Moreover, we report a significant correlation between dysbindin expression level and the phosphorylation level of c-Jun N-terminal kinase (JNK), which is implicated in the regulation of cytoskeletal organization. These findings suggest that dysbindin plays a key role in coordinating JNK signaling and actin cytoskeleton required for neural development. |
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