小胞輸送過程に依存した視細胞変性のメカニズムの解明

• 研究課題/領域番号: 23650173
• 研究種目: 挑戦的萌芽研究
• 配分区分: 基金
• 研究分野: 神経科学一般
• 研究機関: 沖縄科学技術大学院大学
• 研究代表者: 政井 一郎 沖縄科学技術大学院大学, 神経発生ユニット, 准教授 (50242087)
• 連携研究者: 西脇 優子 沖縄科学技術大学院, 神経発生ユニット, 研究員 (20360620)
• 研究期間 (年度): 2011 – 2012
• 研究課題ステータス: 完了 (2012年度)
• 配分額: 3,640千円 (直接経費: 2,800千円、間接経費: 840千円); 2012年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円); 2011年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
• キーワード: 神経科学 / 脳神経疾患 / 視細胞変性 / 遺伝疾患 / アポトーシス / 小胞輸送 / ゼブラフィッシュ / BH3-only蛋白質 / 細胞死 / β-SNAP / BNip1 / BH3蛋白質

研究概要

ヒトでは遺伝性の視細胞変性疾患が知られている。今までの研究から、視細胞変性と小胞輸送の異常との関連が報告されていたが、その背景にあるメカニズムは不明であった。本研究では、魚類であるゼブラフィッシュを用いて、視細胞変性のメカニズムを研究し、小胞輸送の破綻に反応して細胞死を誘導する因子としてBNip1を同定した。この成果は、視細胞変性の原因となる新たな仕組みを提示するだけでなく、ヒトにおける遺伝性網膜疾患の病態理解への貢献も期待できる。

研究成果

• [雑誌論文] The BH3-only SNARE BNip1 mediates photoreceptor apoptosis in response to vesicular fusion defects (2013)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 雑誌名: Developmental Cell 巻: 25 号: 4 ページ: 374-387
  • DOI: 10.1016/j.devcel.2013.04.015
  • 査読あり
• [雑誌論文] (*equal contribution; #corresponding authors) Ectopic expression of the cone-specific Gprotein-coupled receptor kinase GRK7 in zebrafish rods leads to decreased photosensitivity and compromised visual performance (2011)
  • 著者名/発表者名: Vogalis,F., Shiraki,T., Kojima,D., Fukada,Y. & Lamb,T.
  • 雑誌名: J. Physiol. (London) 巻: 589 号: 9 ページ: 2321-2348
  • DOI: 10.1113/jphysiol.2010.204156
  • 査読あり
• [学会発表] Syntaxin18cis-SNARE complex is a novel alarm factorthat detects vesicular transport defects (2013)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: The 46th Annual Meeting of the Japanese Society of Developmental Biologists.
  • 発表場所: Matsue, Shimane Japan
• [学会発表] Characterization of a zebrafish mutantshowing cone photoreceptor degeneration (2013)
  • 著者名/発表者名: Iribarne, M., Nishiwaki, Y., and Masai, I.
  • 学会等名: The 46th Annual Meeting of the Japanese Society of Developmental Biologists Matsue,
  • 発表場所: Shimane, Japan
• [学会発表] Syntaxin18 cis-SNARE complex is a novel alarm factor that detects vesicular transport defects (2013)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: The 46th Annual Meeting of the Japanese Society of Developmental Biologists
  • 発表場所: Matsue, Japan
• [学会発表] Characterization of a zebrafish mutant showing cone photoreceptor degeneration (2013)
  • 著者名/発表者名: Iribarne, M., Nishiwaki, Y., and Masai, I.
  • 学会等名: The 46th Annual Meeting of the Japanese Society of Developmental Biologists
  • 発表場所: Matsue, Japan
• [学会発表] Geneticmutation of beta-SNAP causes photoreceptordegeneration through the activation of theBH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: 10th International Conference Zebrafish Development and Genetics
  • 発表場所: Madison, USA
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: APDBC Taiwan 2012 Asia-Pacific Developmental Biology Conference 2012
  • 発表場所: Taipei Innovation City Convention Center, Taipei, Taiwan
• [学会発表] The BH3-only SNARE of syntaxin18, BNip1, mediates photoreceptor apoptosis in response to vesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: Gordon researchconference ? visual system development.
  • 発表場所: Colby-Sawyer College, New London, NH
• [学会発表] The BH3-onlySNARE of syntaxin18, BNip1, is a mediatorof photoreceptor apoptosis in response tovesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: The 35th annual meeting of the Molecular Biology Society
  • 発表場所: Japan. Fukuoka
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE,BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: The 18th Japanese Medaka and zebrafish meeting.
  • 発表場所: Kyoto, Japan
• [学会発表] The BH3-onlySNARE of syntaxin18, BNip1, is a mediatorof photoreceptor apoptosis in response tovesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: Neuroscience 2012.The 35thannual meeting of the JapanNeuroscience Society.
  • 発表場所: Nagoya, Japan
• [学会発表] Geneticmutation of beta-SNAP causesphotoreceptor degeneration through theactivation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y.,Oguri, E., Nakamura, S., Suzuki, S.,Yuasa-Kawada, J., Kinoshita-Kawada, M.,Mochizuki, T., and Masai, I.
  • 学会等名: Joint meeting of the 45th annual meeting of the Japanese society of DevelopmentalBiologists & the 64thannual meeting of theJapanese society of Cell Biology.
  • 発表場所: Kobe,Japan
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: 10th International Conference Zebrafish Development and Genetics
  • 発表場所: Madison, USA
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: APDBC Taiwan 2012 Asia-Pacific Developmental Biology Conference 2012
  • 発表場所: Taipei, Taiwan
• [学会発表] The BH3-only SNARE of syntaxin18, BNip1, mediates photoreceptor apoptosis in response to vesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: Gordon research conference visual system development
  • 発表場所: New London, USA
• [学会発表] The BH3-only SNARE of syntaxin18, BNip1, is a mediator of photoreceptor apoptosis in response to vesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: The 35th annual meeting of the Molecular Biology Society of Japan
  • 発表場所: Fukuoka, Japan
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: The 18th Japanese Medaka and zebrafish meeting
  • 発表場所: Kyoto, Japan
• [学会発表] The BH3-only SNARE of syntaxin18, BNip1, is a mediator of photoreceptor apoptosis in response to vesicular fusion defects (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: The 35th annual meeting of the Japan Neuroscience Society
  • 発表場所: Nagoya, Japan
• [学会発表] Genetic mutation of beta-SNAP causes photoreceptor degeneration through the activation of the BH3-only SNARE, BNip1 (2012)
  • 著者名/発表者名: Nishiwaki, Y., Yoshizawa, A., Kojima, Y., Oguri, E., Nakamura, S., Suzuki, S., Yuasa-Kawada, J., Kinoshita-Kawada, M., Mochizuki, T., and Masai, I.
  • 学会等名: Joint meeting of the 45th annual meeting of the Japanese society of Developmental Biologists & the 64th annual meeting of the Japanese society of Cell Biology
  • 発表場所: Kobe, Japan
• [学会発表] Molecular mechanism that transforms defects in intracellular vesicular transport into apoptosis in zebrafishphotoreceptors (2011)
  • 著者名/発表者名: Masai, I.
  • 学会等名: 5th Asia-Oceania zebrafish international meeting, China National Convention Center
  • 発表場所: Beijing, China
• [学会発表] Mutation of beta-SNAP induces amitochondria-dependent apoptosis inzebrafish photoreceptors (2011)
  • 著者名/発表者名: Nishiwaki, Y., Suzuki, S., Yoshizawa, A.,Kojima, Y., Mochizuki, T., Masai, I.
  • 学会等名: 7th EuropeanZebrafish Meeting
  • 発表場所: Edinburgh, Scotland
• [学会発表] Azebrafish corona mutation induces aBcl2-dependent apoptosis in photoreceptor (2011)
  • 著者名/発表者名: Nishiwaki, Y., Suzuki, S., Yoshizawa, A.,Kojima, Y., Mochizuki, T., Masai, I.
  • 学会等名: 44th Annual Meeting of the Japanese Society of Developmental Biologists
  • 発表場所: Okinawa Convention Center (Ginowan City)
• [学会発表] Molecular mechanism that transforms defects in intracellular vesicular transport into apoptosis in zebrafish photoreceptors (2011)
  • 著者名/発表者名: 政井一郎
  • 学会等名: 第5回 アジアオセアニア ゼブラフィッシュ国際会議
  • 発表場所: 北京、中国
• [学会発表] A zebrafish corona mutation induces a Bcl2-dependent apoptosis in photoreceptor (2011)
  • 著者名/発表者名: 西脇優子、鈴木祥平、吉澤あすか、小島豊、望月俊昭、政井一郎
  • 学会等名: 第44回 日本発生生物学会年会
  • 発表場所: 沖縄、日本
• [学会発表] Mutation of beta-SNAP induces a mitochondria-dependent apoptosis in zebrafish photoreceptors (2011)
  • 著者名/発表者名: 西脇優子、鈴木祥平、吉澤あすか、小島豊、望月俊昭、政井一郎
  • 学会等名: 第7回 ヨーロッパ ゼブラフィッシュ国際会議
  • 発表場所: エジンバラ、英国
• [備考] 目の見えないゼブラフィッシュがヒトの網膜疾患治療に光をもたらす
  • URL: http://www.oist.jp/ja/news-center/press-releases/10744