Autophagic neurodegeneration in molecular pathogenesis of chorea-accanthocytosis

• Project/Area Number: 23390291
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kagoshima University
• Principal Investigator: SANO Akira 鹿児島大学, 医歯(薬)学総合研究科, 教授 (30178800)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Masayuki 鹿児島大学, 大学院・歯学総合研究科, 准教授 (90332832)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2012: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 有棘赤血球舞踏病 / chorein / オートファジー / α-tubulin / 脱アセチル化 / 微小管 / VPS13A / 免疫沈降 / 免疫細胞化学 / HEK293細胞 / 結合タンパク質 / 結合蛋白質 / 免疫組織化学 / マクロオートファジー / ミトファジー

Research Abstract

Co-immunopreticipation assay using extracts from chorein-overexpressing cells showed that chorein, the protein responsible for chorea-acanthocytosis (ChAc), co-precipitated with alpha-tubulin and HDAC6, probably leading to facilitation of alpha-tubulin deacetylation. Cell viability assay revealed that cells stably expressing chorein, significantly preserved cell viability during nutrient deprivation. These results suggest that chorein interacts with the cytoskeletal proteins and may play an important role in autophagic process, including in the protection against starvation-induced cell damages. Disruption of this cell protection mechanism may involved in molecular pathogenesis of ChAc.

Research Products

• [Journal Article] Chorein, the proTein responsible for chorea-acanthocytosis, interacts with β-adducin and β-actin (2013)
  • Author(s): Shiokawa N, Nakamura M, SameShima M, Deguchi A, Hayashi T, Sasaki N, Sano A
  • Journal Title: Biochem Biophys res Commun Volume: 441 Issue: 1 Pages: 96-101
  • DOI: 10.1016/j.bbrc.2013.10.011
  • Peer Reviewed
• [Journal Article] Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances (2012)
  • Author(s): Sangatsuda Y, Nakamura M, Tomiyasu A, Deguchi A Toyota Y, Goto Y, Nishino I, Ueno S, Sano A
  • Journal Title: Mitochondrion Volume: 12 Issue: 6 Pages: 617-622
  • DOI: 10.1016/j.mito.2012.10.002
  • Peer Reviewed
• [Journal Article] Subcellular localization and putative role of VPS13A/chorein in dopaminergic neuronal cells (2012)
  • Author(s): Hayashi T., et al
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 419巻 Issue: 3 Pages: 511-516
  • DOI: 10.1016/j.bbrc.2012.02.047
  • Peer Reviewed
• [Journal Article] Novel pathogenic mutations and copy number variations in the VPS13A Gene in patients with chorea-acanthocytosis (2011)
  • Author(s): Tomiyasu A, Nakamura M, Ichiba M, et al
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 156 Issue: 5 Pages: 620-631
  • DOI: 10.1002/ajmg.b.31206
  • Peer Reviewed
• [Journal Article] Comprehensive analysis of the genes responsible for neuroacanthocytosis in mood disorder and schizophrenia (2011)
  • Author(s): Shimo H, Nakamura M, Tomiyasu A, Ichiba M, Ueno SI, Sano A
  • Journal Title: Neurosci. Res Volume: 69 Issue: 3 Pages: 196-202
  • DOI: 10.1016/j.neures.2010.12.001
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA deletion mutations in patients with neuropsychiatric symptoms (2011)
  • Author(s): Kato M, Nakamura M, Ichiba M, Tomiyasu A, Shimo H, Higuchi I, Ueno S, Sano A
  • Journal Title: Neurosci Res Volume: 69 Issue: 4 Pages: 331-336
  • DOI: 10.1016/j.neures.2010.12.013
  • Peer Reviewed
• [Journal Article] Familial Semantic Dementia with P301L Mutation in the Tau Gene (2011)
  • Author(s): Ishizuka T, Nakamura M, Ichiba M, et al
  • Journal Title: Dement Geriatr Cogn Disord Volume: 31 Issue: 5 Pages: 334-340
  • DOI: 10.1159/000328412
  • Peer Reviewed
• [Journal Article] Chronological changes in prosaposin in the developing rat brain (2011)
  • Author(s): Xue, et al
  • Journal Title: Neurosci Res Volume: 71 Issue: 1 Pages: 22-34
  • DOI: 10.1016/j.neures.2011.06.001
  • Peer Reviewed
• [Journal Article] Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive exteraal ophthalmoplegia (2011)
  • Author(s): Takata A, Kato M, Nakamura M, et al
  • Journal Title: Genom Biol Volume: 12 Issue: 9
  • DOI: 10.1186/gb-2011-12-9-r92
  • Peer Reviewed
• [Journal Article] Remapping and mutation analysis of benign adult familial myoclonic epilepsy in a Japanese pedigree (2011)
  • Author(s): Mori S, Nakamura M, Yasuda T, et al
  • Journal Title: Jounal of Human Genetics Volume: 56 Issue: 10 Pages: 743-747
  • DOI: 10.1038/jhg.2011.93
  • NAID: 10030661426
  • Peer Reviewed
• [Presentation] Chorein interacts with cytoskeletal proteins on nutrient starvation HEK293 cells (2013)
  • Author(s): Sasaki N, Nakamura M, Shiokawa N, Deguchi A, Sano A
  • Organizer: The 56th Meeting of the japanese Society for Neurochemistry
  • Place of Presentation: Kyoto Japan
• [Presentation] Identification of Binding partners of horein (2013)
  • Author(s): Shiokawa N, Nakamura M, Deguchi A, Sasaki N, Sano A
  • Organizer: The 56th Meeting of the japanese Society for Neurochemistry
  • Place of Presentation: Kyoto Japan
• [Presentation] Chorein interacts with cytoskeletal proteins in HEK293 cells treated with achemical inhibitor of oxidative phosphorylation (2013)
  • Author(s): Deguchi A, Nakamura M, Shiokawa N, Sasaki N, Sano A
  • Organizer: The 56th Meeting of the japanese Society for Neurochemistry
  • Place of Presentation: Kyoto Japan
• [Presentation] Chorein interacts with cytoskeletal proteins in HEK293 cells treated with a chemical inhibitor of oxidative phosphorylation. (2013)
  • Author(s): Deguchi A, Nakamura M, Shiokawa N, Sasaki N, Sano A
  • Organizer: The 56th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 京都
• [Presentation] Identification of binding partners of chorein. (2013)
  • Author(s): Shiokawa N, Nakamura M, Deguchi A, Sasaki N, Sano A
  • Organizer: The 56th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 京都
• [Presentation] Chorein interacts with cytoskeletal proteins on nutrient starvation in HEK293 cells. (2013)
  • Author(s): Sasaki N, Nakamura M, Shiokawa N, Deguchi A, Sano A
  • Organizer: The 56th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: 京都
• [Presentation] Chorein interacts with cytoskeletal proteins on nutrient starvation in HEK293 cells. (2013)
  • Author(s): N. Sasaki, M. Nakamura, N. Shiokawa, A. Deguchi, A. Sano
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
• [Presentation] Chrein interacts with cytoskeltalprotein interacts with cytoskeltal proteins in HEK293 cells (2012)
  • Author(s): Deguchi A, Nakamura M, Shiokawa N, Sasaki N, Sano A
  • Organizer: 11th biennial meeting of the Asian Pacific Society for Neurochemistry/55th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe Japan
• [Presentation] Proteomics approach to identify chorein-interacting proteins (2012)
  • Author(s): Shiokawa N, Nakamura M, Sameshima M, Deguchi A, Sano A
  • Organizer: 11th biennial meeting of the Asian Pacific Society for Neurochemistry/55th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe Japan
• [Presentation] Chorein is involved in exocytosis of dene core vesicles in differentiated PC12 cells (2012)
  • Author(s): Hayashi T, Kishida M, Nishizawa Y, Lijima M, Koriyama C, Nakamura M, Sano A, Kishida S
  • Organizer: 11th biennial meeting of the Asian Pacific Society for Neurochemistry/55th Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe Japan
• [Presentation] 舞踏病原因遺伝子VPS13A変異による精神障害発症機構 (2011)
  • Author(s): 佐野輝
  • Organizer: 第54回日本神経化学会年会シンポジウム
  • Place of Presentation: 石川県山代温泉瑠璃光
  • Year and Date: 2011-09-26
• [Presentation] 舞踏病原因遣伝子VPS13A変異による精神障害発症機構 (2011)
  • Author(s): 佐野 輝
  • Organizer: 第54回日本神経化学会年会 シンポジウム「精神障害の新規分子について-最近の知見から-」
  • Place of Presentation: 石川
• [Book] 脳とこころのプライマリケア2巻 知能と衰え VII章 認知症各論(Huntington 病, 歯状核赤核淡蒼球ルイ体萎縮症, 有棘赤血球踏病) (2013)
  • Author(s): 中村雅之, 佐野 輝
  • Publisher: シナジー
• [Book] 脳とこころのプライマリケア2巻 知能と衰え VII章 認知症各論 (Huntington病, 歯状核赤核淡蒼球ルイ体萎縮症, 有棘赤血球舞踏病) (2013)
  • Author(s): 中村雅之、佐野 輝
  • Total Pages: 7
  • Publisher: シナジー
• [Book] 症候群ハンドブック(5. 有棘赤血球を伴う舞踏病) (2011)
  • Author(s): 中村雅之, 佐野 輝
  • Publisher: 中山書店
• [Book] 症候群ハンドブック(分担部分:有棘赤血球を伴う舞踏病) (2011)
  • Author(s): 中村雅之、佐野輝
  • Publisher: 中山書店(総編集:井村裕夫、編集:福井次矢/辻省次)
• [Book] 現代精神医学辞典(分担部分:クリューヴアー=ビュージー症候群、神経化学、進行性ミオクローヌスてんかん、トリヌクレオチドリピート、ハンチントン病、ヒョレアアカントサイトーシス、ヒョレア症候群、ファール病、ペラグラ精神病、ミトコンドリア脳筋症) (2011)
  • Author(s): 佐野輝
  • Total Pages: 12
  • Publisher: 弘文堂(神庭重信、中谷陽二、武田雅俊、鹿島晴雄、狩野力八郎、市川宏伸編集)
• [Remarks]
  • URL: http://www.kufm.kagoshima-u.ac.jp/~np/