Figure of true clathrin-dependent intracellular vesicle transport

• Project/Area Number: 24570159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Nara Women's University
• Principal Investigator: WATANABE Toshio 奈良女子大学, 自然科学系, 教授 (60201208)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 小胞輸送 / Arf1 / CALM / SMAP1 / SMAP2 / CALM-AF10 / 核外排出配列NES / アルツハイマー症

Outline of Final Research Achievements

With the aim to present a "figure of true clathrin-dependent intracellular vesicle transport", a detailed analysis of Arf1, CALM, and SMAP was performed using a knockout mouse. Arf1 KO mice is embryonic lethal, thus there was no complementation with other family members. For detailed analysis, Arf1 KO MEF cells were established. We discover the pale eye color of the CALM KO embryos, thus CALM is found likely to be involved in the accumulation of melanin. CALM is also found to be involved in to degradation of the up-taken c-kit tyrosine kinase receptor. Mice doubly-deficient in the Arf GAPs SMAP1 and SMAP2 exhibit embryonic lethality.

Research Products

• [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA (2015)
  • Author(s): Hayashi K, Momoi Y , Tanuma N, Kishimoto A, Ogoh H, Kato H, Suzuki M, Sakamoto Y, Inoue Y, Nomura M, Kiyonari H, Sakayori M, Fukamachi K, Kakugawa Y, Yamashita Y, Ito S, Sato I, Suzuki A, Nishio M, Suganuma M, Watanabe T, and Shima H
  • Journal Title: Oncogene Volume: 印刷中 Issue: 35 Pages: 4647-55
  • DOI: 10.1038/onc.2014.398
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clathrin assembly protein CALM Plays a Critical Role in KIT Signaling by Regulating Its Cellular Transport from Early to Late Endosomes in Hematopoietic Cells. (2014)
  • Author(s): Shinya Rai, Hirokazu Tanaka*, Mai Suzuki , Honami Ogoh, Yasuhiro Taniguchi, Yasuyoshi Morita, Takahiro Shimada, Akira Tanimura, Keiko Matsui, Takafumi Yokota, Kenji Oritani, Kenji Tanabe, Toshio Watanabe, Yuzuru Kanakura, and Itaru Matsumura
  • Journal Title: PLoS ONE Volume: 該当しない Issue: 10 Pages: 0109441-0109441
  • DOI: 10.1371/journal.pone.0109441
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The ADP-ribosylation factor 1 gene is indispensable for mouse embryonic development after implantation (2014)
  • Author(s): Natsuki Hayakawa**, Honami Ogoh**, Mami Sumiyoshi**, Kananko Miyamoto, Yasuhisa Matsui, Saori Nishikawa, Yuko Maede, Hiroshi Kiyonari, Mai Suzuki, and Toshio Watanabe
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 453 Pages: 748-753
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia. (2014)
  • Author(s): 鈴木 麻衣
  • Journal Title: Cancer Science Volume: 105 Issue: 3 Pages: 315-323
  • DOI: 10.1111/cas.12347
  • Peer Reviewed
• [Journal Article] Decreased CALM expression reduces Aβ42 production ratio through clathrin-mediated endocytosis of Y-secretase. (2014)
  • Author(s): 金津 邦彦
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3386-3386
  • DOI: 10.1038/ncomms4386
  • Peer Reviewed
• [Journal Article] SMAP2 Regulates Retrograde Transport from Recycling Endosomes to the Golgi. (2013)
  • Author(s): Matsudaira T., Uchida Y., Tanabe K., Kon S., Watanabe T., Taguchi T. and Arai H.
  • Journal Title: PLoS ONE Volume: 8 Issue: 7 Pages: e69145-e69145
  • DOI: 10.1371/journal.pone.0069145
  • Peer Reviewed / Open Access
• [Journal Article] The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis. (2013)
  • Author(s): Funaki T, Kon S, Tanabe K, Natsume W, Sato S, Shimizu T, Yoshida N, Wong WF, Ogura A, Ogawa T, Inoue K, Ogonuki N, Miki H, Mochida K, Endoh K, Yomogida K, Fukumoto M, Horai R, Iwakura Y, Ito C, Toshimori K, Watanabe T, Satake M.
  • Journal Title: Mol. Biol. Cell Volume: 24 Issue: 17 Pages: 2633-44
  • DOI: 10.1091/mbc.e13-05-0234
  • Peer Reviewed
• [Journal Article] SMAP1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. (2013)
  • Author(s): S Kon, N Minegishi, K Tanabe, T Watanabe, T Funaki, W F Wong, D Sakamoto, Y Higuchi, H Kiyonari, K Asano, Y Iwakura, M Fukumoto, M Osato, M Sanada, S Ogawa, T Nakamura and M Satake
  • Journal Title: Journal of Clinical Investigation Volume: 123 Pages: 1123-1137
  • Peer Reviewed
• [Journal Article] Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line. (2012)
  • Author(s): Mai Suzuki, Davor Solter, and Toshio Watanabe.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 418 Pages: 439-444
  • Peer Reviewed
• [Journal Article] The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice. (2012)
  • Author(s): 鈴木 麻衣
  • Journal Title: PLoS ONE Volume: 7 Issue: 2 Pages: 31854-31854
  • DOI: 10.1371/journal.pone.0031854
  • Peer Reviewed
• [Presentation] クラスリン集合タンパク質CALM欠損が及ぼすメラニン産生への影響。 (2015)
  • Author(s): 大野絹代, 増田成美, 小河穂波,住吉麻実,早川夏姫, 稲垣綾華, 大塚瑞希, 中尾知美, 鈴木麻衣, 田中宏和, 森田詠子, 酒井良明, 渡邊利雄
  • Organizer: 第62回 日本生化学会近畿支部例会
  • Place of Presentation: 草津、滋賀県
  • Year and Date: 2015-05-16
• [Presentation] 融合遺伝子による白血病幹細胞の制御機構。 (2014)
  • Author(s): 鈴木 麻衣、山形 和恒、齋藤 眞理子、渡邊 利雄、北林 一生
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-27
  • Invited
• [Presentation] SMAP（Small Arf GAP）1,2両遺伝子欠損胚は致死でアポトーシスを起こしている。 (2014)
  • Author(s): 住吉麻実、小河穂波、早川夏姫、鈴木麻衣、松居靖久、渡邊利雄
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25
• [Presentation] CALM-AF10の白血病誘導にはCALMが有する核外移行シグナルの機能が必須である。 (2014)
  • Author(s): 鈴木 麻衣, 篠 実花, 相川 祐規子, 渡邊 利雄, 北林 一生
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] 遺伝学的アルツハイマー病予防因子PICALM/CALMが病態形成に寄与する分子機構の解明。 (2014)
  • Author(s): 金津 邦彦, 渡邊 利雄, 岩坪 威, 富田 泰輔
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] CALM LINKS CYTOKINE SIGNALS TO HEMATOPOIETIC CELL GROWTH AND SURVIVAL BY REGULATING INTRACELLULAR TRAFFICKING OF RECEPTOR TYROSINE KINASES. (2013)
  • Author(s): Shinya Rai, Hirokazu Tanaka, Mai Suzuki, Akira Tanimura, Keiko Matsui, Toshio Watanabe, Yuzuru Kanakura, Itaru Matsumura.
  • Organizer: 18th Congress of the European Hematology Association
  • Place of Presentation: Stockholm, Sweden
• [Presentation] CALM-AF10のCALM部分はどのように白血病発症へ関与するか (2013)
  • Author(s): 鈴木麻衣、篠実花、相川祐規子、田中宏和、松村到、金倉譲、北林一生、渡邊利雄
  • Organizer: 第17回 造血器腫瘍研究会
  • Place of Presentation: 宮崎
• [Presentation] CALM-AF10融合遺伝子のCALMによる白血病発症と赤血球造血への役割 (2013)
  • Author(s): 鈴木麻衣、田中宏和、松村到、金倉譲、北林一生、渡邊利雄
  • Organizer: 個体レベルのがん研究ワークショップ
  • Place of Presentation: 大津
  • Invited
• [Presentation] SMAP（Small Arf GAP）1,2両遺伝子欠損胚は致死である。 (2012)
  • Author(s): 原華苗、今井恵理、鈴木麻衣、昆俊介、田邊賢司、船木智、佐竹正延、松居靖久、渡邊利雄
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 博多
• [Presentation] クラスリン集合因子CALMの欠損はトランスフェリンを介した鉄の取り込みを減少させ造血障害を起こす (2012)
  • Author(s): 鈴木麻衣、田中宏和、谷村朗、田邊賢司、大江夏子、頼 晋也、昆俊亮、福本学、竹居孝二、松村到、金倉譲、渡邊利雄
  • Organizer: 【第35回日本分子生物学会年会】ワークショップ
  • Place of Presentation: 博多
  • Invited
• [Presentation] Nuclear export signal (NES) within CALM is necessary for CALM-AF10-mediated leukemic transformation.
  • Author(s): 鈴木麻衣、篠実花、相川祐規子、渡邊利雄、北林一生
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] SMAP（Small Arf GAP）1, 2両遺伝子欠損MEF細胞株の樹立
  • Author(s): 住吉麻実、原華苗、小河穂波、鈴木麻衣、昆俊介、田邊賢司、佐竹正延、田沼延公、島礼、渡邊利雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 小胞形成開始因子のArf1 conditional ノックアウトマウスの作製。
  • Author(s): 生田優希、早川夏姫、小河穂波、鈴木麻衣、阿部高也、清成寛、相沢慎一、渡邊利雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 小胞形成開始因子Arf1を欠損した胚盤胞のin vitro培養下での増殖解析。
  • Author(s): 早川夏姫、生田優希、小河穂波、住吉麻実、原華苗、鈴木麻衣、渡邊利雄
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] SMAP2はリサイクリングエンドソームからゴルジ体への物質輸送を制御する。
  • Author(s): 松平竜之、田邊賢司、渡邊利雄、田口友彦、新井洋由
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] GTP脱リン酸化酵素のARFとその活性化因子SMAPの欠損マウス解析。
  • Author(s): 住吉麻美、早川夏姫、小河穂波、西川紗織、鈴木麻衣、昆俊介、佐竹正延、田邊賢司、田沼延公、島礼、渡邊利雄
  • Organizer: 第6回 日本プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 津
• [Book] 史上最強図解 これならわかる！分子生物学最 (2013)
  • Author(s): 渡邊利雄
  • Total Pages: 296
  • Publisher: ナツメ社
• [Remarks] 不明であった皮膚がんを抑え込む機構を解明
  • URL: http://www.nara-wu.ac.jp/news/H26news/20141209/20141209.html
• [Remarks] わかったぞ、皮膚がん抑制の仕組み
• [Remarks] アルツハイマー病発症を予防する因子CALMの機能を解明
  • URL: http://www.nara-wu.ac.jp/news/H25news/20140303.htm
• [Remarks] 従来の理解を覆す新規の「白血病」発症機構を発見
  • URL: http://www.nara-wu.ac.jp/news/H25news/20140228/20140228.htm
• [Remarks] 奈良女子大学 理学部 生物科学科
  • URL: http://www.nara-wu.ac.jp/rigaku/bio/index.html