Deciphering the role of protrudin regulating neuronal vesicular transport

• Project/Area Number: 22240038
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kyushu University
• Principal Investigator: NAKAYAMA Keiichi 九州大学, 生体防御医学研究所, 教授 (80291508)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000); Fiscal Year 2012: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2011: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000); Fiscal Year 2010: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
• Keywords: 神経 / 細胞内輸送 / 低分子Gタンパク質 / シナプス / 高次脳機能 / 低分子GTP結合タンパク質

Research Abstract

We investigated the structure-function relationship of protrudin that regulates intracellular vesicle transport in neurons. Protrudin interacts with Rab11 through the RBD11 domain, with VAP and KIF5 through the FFAT motif, and sulfatide and PI(5)P through the atypical FYVE domain. We also created mice deficient in protrudin and found that anatomical and physiological alterations in the mutant mice, suggesting that protrudin contributes to vesicular trafficking in neuronal cells

Research Products

• [Journal Article] Ablation of fbxw7 eliminates leukemia-initiating cells by preventing quiescence (2013)
  • Author(s): Takeishi, S., Matsumoto, A., Onoyama, I., Naka, K., Hirao, A., Nakayama, K. I
  • Journal Title: Cancer Cell Volume: 23 Pages: 347-361
• [Journal Article] Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression (2013)
  • Author(s): Reavie, L., Buckley, S. M., Loizou, E., Takeishi, S., Aranda-Orgilles, B., Ndiaye-Lobry, D., Abdel-Wahab, O., Ibrahim, S., Nakayama, K. I., Aifantis, I
  • Journal Title: Cancer Cell Volume: 23 Pages: 362-375
• [Journal Article] FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes (2013)
  • Author(s): Hirano, A., Yumimoto, K., Tsunematsu, R., Matsumoto, M., Oyama, M., Kozuka-Hata, H., Nakagawa, T., Lanjakornsiripan, D., *Nakayama, K. I., Fukada, Y. (Co-corresponding authors)
  • Journal Title: Cell Volume: 152 Pages: 1106-1118
• [Journal Article] Selective escape of proteins from the mitochondria during mitophagy (2013)
  • Author(s): Saita, S., Shirane, M., Nakayama, K. I.
  • Journal Title: Nature Commun. Volume: 4 Pages: 1410-1410
• [Journal Article] Selective escape of proteins from mitochondria during mitophagy (2013)
  • Author(s): Saita, et al
  • Journal Title: Nature Communications Volume: 29(web) Issue: 1 Pages: 1410-1423
  • DOI: 10.1038/ncomms2400
  • Peer Reviewed
• [Journal Article] Ablation of fbxw7 eliminates leukemia-initiating cells by preventing quiescence. (2013)
  • Author(s): Takeishi S
  • Journal Title: Cancer Cell Volume: 23 Issue: 3 Pages: 347-361
  • DOI: 10.1016/j.ccr.2013.01.026
  • Peer Reviewed
• [Journal Article] FBXL21 Regulates Oscillation of the Circadian Clock through Ubiquitination and Stabilization of Cryptochromes (2013)
  • Author(s): Arisa Hirano, Kanae Yumimoto, Ryosuke Tsunematsu, Masaki Matsumoto, Masaaki Oyama, Hiroko Kozuka-Hata, Tomoki Nakagawa, Darin Lanjakornsiripan, Keiichi I. Nakayama, and Yoshitaka Fukada
  • Journal Title: Cell Volume: 152 Issue: 5 Pages: 1106-1118
  • DOI: 10.1016/j.cell.2013.01.054
  • Peer Reviewed
• [Journal Article] Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression. (2013)
  • Author(s): Reavie L
  • Journal Title: Cancer Cell Volume: 23 Issue: 3 Pages: 362-375
  • DOI: 10.1016/j.ccr.2013.01.025
  • Peer Reviewed
• [Journal Article] UPS delivers pluripotency (2012)
  • Author(s): Okita, Y., Nakayama, K. I.
  • Journal Title: Cell Stem Cell Volume: 11 Pages: 728-730
• [Journal Article] The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis (2012)
  • Author(s): Chan, C. H., Li, C. F., Yang, W. L., Gao, Y., Lee, S. W., Feng, Z., Huang, H. Y., Tsai, K. K., Flores, L. G., Shao, Y., Hazle, J. D., Yu, D., Wei, W., Sarbassov, D., Hung, M. C., Nakayama, K. I., Lin, H. K.
  • Journal Title: Cell Volume: 149 Pages: 1098-1111
• [Journal Article] The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, Herceptin sensitivity and tumorigenesis (2012)
  • Author(s): Chan CH.,Li CF., Yang WL., Gao Y., Lee SW., Feng Z., Huang HY., Tsai KKC., Flores LG., Shao Y., Hazle JD., Yu D., Wei W., Sarbassov D., Hung MC., Nakayama KL., Lin HK.
  • Journal Title: Cell Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] p57 is required for quiescence and maintenance of adult hematopoietic stem cells (2011)
  • Author(s): Matsumoto, A., Takeishi, S., Kanie, T., Susaki, E., Onoyama, I., Tateishi, Y., Nakayama, K., Nakayama, K. I.
  • Journal Title: Cell Stem Cell Volume: 9 Pages: 262-271
• [Journal Article] The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo (2011)
  • Author(s): Moroishi, T., Nishiyama, M., Takeda, Y., Iwai, K., Nakayama, K. I.
  • Journal Title: Cell Metab. Volume: 14 Pages: 339-351
• [Journal Article] Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation (2011)
  • Author(s): Matsuzaki, F., Shirane, M., Matsumoto, M., Nakayama, K. I.
  • Journal Title: Mol. Biol. Cell Volume: 22 Pages: 4602-4620
• [Journal Article] p57Kip2 and p27Kip1 cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70 (2011)
  • Author(s): Zou, P., Yoshihara, H., Hosokawa, K., Tai, I., Shinmyozu, K., Tsukahara, F., Maru, Y., Nakayama, K., Nakayama, K. I., Suda, T.
  • Journal Title: Cell Stem Cell Volume: 9 Pages: 247-261
• [Journal Article] Deficiency of Rap1-binding protein RAPL causes lymphoproliferative disorders through mislocalization of p27kip1 (2011)
  • Author(s): Katagiri, K., Ueda, Y., Tomiyama, T., Yasuda, K., Toda, Y., Ikehara, S., Nakayama, K. I., Kinashi, T.
  • Journal Title: Immunity Volume: 34 Pages: 24-38
• [Journal Article] Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J. Clin. Inves (2011)
  • Author(s): Onoyama, I., Suzuki, A., Matsumoto, A., Tomita, K., Katagiri, H., Oike, Y., Nakayama, K., Nakayama, K. I
  • Journal Title: J. Clin. Invest. Volume: 121 Pages: 342-354
• [Journal Article] Spyracopoulos, L., Leng, R. P.: UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53 (2011)
  • Author(s): Wu, H., Pomeroy, S. L., Ferreira, M., Teider, N., Mariani, J., Nakayama, K. I., Hatakeyama, S.
  • Journal Title: Nature Med. Volume: 17 Pages: 347-355
• [Journal Article] SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction (2011)
  • Author(s): Inuzuka, H., Shaik, S., Onoyama, I., Gao, D., Tseng, A., Maser, R. S., Zhai, B., Wan, L., Gutierrez, A., Lau, A. W., Xiao, Y., Christie, A. L., Aster, J., Settleman, J., Gygi, S. P., Kung, A. L., Look, T., Nakayama, K. I., DePinho, R. A., Wei, W.
  • Journal Title: Nature Volume: 471 Pages: 104-109
• [Journal Article] The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo (2011)
  • Author(s): Moroishi T., Nishiyama M., Takeda Y., Iwai K., Nakayama KI.
  • Journal Title: Cell Metabolism Volume: 14 Issue: 3 Pages: 339-351
  • DOI: 10.1016/j.cmet.2011.07.011
  • Peer Reviewed
• [Journal Article] Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. (2011)
  • Author(s): Onoyama, I., Suzuki, A., Matsumoto, A., Tomita, K., Katagiri, H., Oike, Y., Nakayama, K., Nakayama, K.I.
  • Journal Title: J.Clin.Invest. Volume: 121 Pages: 342-354
  • Peer Reviewed
• [Journal Article] SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquity lation and destruction. (2011)
  • Author(s): Inuzuka, H., Shaik, S., Onoyama, I., Gao, D., Tseng, A., Maser, R.S., Zhai, B., Wan, L., Gutierrez, A., Lau, A.W., Xiao, Y., Christie, A.L., Aster, J., Settleman, J., Gygi, S.P., Kung, A.L., Look, T., Nakayama, K.I., DePinho, R.A., Wei, W.
  • Journal Title: Nature Volume: 471 Pages: 104-109
  • Peer Reviewed
• [Journal Article] Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis (2010)
  • Author(s): Chan, C. H., Lee, S. W., Li, C. F., Wang, J., Yang, W. L., Wu, C. Y., Wu, J., Nakayama, K. I., Kang, H. Y., Huang, H. Y., Hung, M. C., Pandolfi, P. P., Lin, H. K.
  • Journal Title: Nature Cell Biol. Volume: 12 Pages: 457-467
• [Journal Article] KDM7 is a dual demethylase for histone H3 lysines 9 and 27 and functions in brain development (2010)
  • Author(s): Tsukada, Y., Ishitani, T., Nakayama, K. I.
  • Journal Title: Genes Dev. Volume: 24 Pages: 432-437
• [Journal Article] Increased E4 activity in mice leads to ubiquitin-containing aggregates and degeneration of hypothalamic neurons resulting in obesity (2010)
  • Author(s): Susaki, E., Kaneko-Oshikawa, C., Miyata, K., Tabata, M., Yamada, T., Oike, Y., Katagiri, H., Nakayama, K.I.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 15538-15547
  • Peer Reviewed
• [Presentation] Next-generation proteomics uncovers the secret of cancer (2013)
  • Author(s): Nakayama, K. I
  • Organizer: Organelle Homeostasis Research Center
  • Place of Presentation: Kick-off Symposium. Fukuoka
  • Year and Date: 2013-03-22
• [Presentation] Next-generation proteomics uncovers the secret of cancer (2013)
  • Author(s): Nakayama KI.
  • Organizer: Organelle Homeostasis Research Center: Kick-off Symposium
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Comprehensive and unbiased identification of substrates for ubiquitin ligases by differential proteomics analysis (2012)
  • Author(s): Nakayama, K. I
  • Organizer: HUPO 2012 11th World Congress
  • Place of Presentation: Boston, MA
  • Year and Date: 2012-12-09
• [Presentation] Cell cycle, metabolism, and signal transduction in cancer revealed by next-generation proteomics (2012)
  • Author(s): Nakayama, K. I
  • Organizer: cer revealed by next-generation proteomics. 2012 American Association for Cancer Research Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-03-31
• [Presentation] ユビキチン化による鉄代謝制御機構とその破綻 (2012)
  • Author(s): 中山 敬一
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 正常幹細胞と癌幹細胞におけるG0期維持機構："G0期追出し療法"による癌根治の可能性 (2012)
  • Author(s): 中山 敬一
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Road to absolute quantification of all human proteins by large-scale targeted proteomics (2011)
  • Author(s): 中山敬一、松本雅記
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2011-12-14
• [Presentation] Road to Human Proteome Project: Absolute quantification of all human proteins by large-scale targeted proteomics (2011)
  • Author(s): Nakayama, K. I
  • Organizer: France-Japan Cancer Meeting
  • Place of Presentation: France-Japan Cancer Meeting
  • Year and Date: 2011-11-24
• [Presentation] Road to absolute quantification of all human proteins by large-scale targeted proteomics (2011)
  • Author(s): Nakayama, K. I
  • Organizer: The 5th International Workshop on Cell Regulations in Division and Arrest
  • Place of Presentation: Onna, Okinawa, Japan
  • Year and Date: 2011-10-26
• [Presentation] Comprehensive and unbiased identification of substrates for ubiquitin ligases by differential proteomic analysis (2011)
  • Author(s): Nakayama, K. I., Yumimoto, K., Matsumoto, M., Oyamada, K., Moroishi, T
  • Organizer: Cold Spring Harbor Symposium "The Ubiquitin Family"
  • Place of Presentation: Cold Spring Harbor, NY
  • Year and Date: 2011-05-08
• [Presentation] Comprehensive elucidation of enzyme-substrate relationship by proteomics: Say good-bye to western blotting (2010)
  • Author(s): Nakayama, K. I., Yumimoto, K., Matsumoto, M
  • Organizer: 6th Global-COE International Symposium: NewHorizons for Modern Science - Biology and Medicine at the Crossroads
  • Place of Presentation: Fukuoka.
  • Year and Date: 2010-08-19
• [Presentation] Comprehensive elucidation of enzyme-substrate relationship by proteomics : Say good-bye to western blotting. (2010)
  • Author(s): Nakayama, K.I., Yumimoto, K., Matsumoto, M.
  • Organizer: 6th Global-COE International Symposium : New Horizons for Modern Science-Biology and Medicine at the Crossroads
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2010-08-19
• [Book] 疾患モデルの作製と利用ーがん (2012)
  • Author(s): 沖田康孝, 中山敬一
• [Book] タンパク質分解. イラストで徹底理解するシグナル伝達キーワード事典 (2012)
  • Author(s): 中山敬一, 蟹江共春
  • Publisher: 羊土社
• [Book] ユビキチン. 生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 諸石寿朗, 中山敬一
• [Book] プロテオミクスが拓く細胞周期研究. 細胞周期フロンティア (2010)
  • Author(s): 松本雅記, 中山敬一
  • Publisher: 共立出版
• [Book] G0期とその周辺:細胞周期の停止と再増殖の分子メカニズム (2010)
  • Author(s): 洲崎悦生, 中山敬一
  • Publisher: 共立出版
• [Book] 創薬・タンパク質研究のためのプロテオミクス解析 (2010)
  • Author(s): 松本雅記, 中山敬一
  • Publisher: 羊土社
• [Book] プロテオミクスが拓く細胞周期研究 (2010)
  • Author(s): 松本雅記、中山敬一
  • Total Pages: 6
  • Publisher: 共立出版,東京
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/saibou/index.html
• [Remarks] 九州大学生体防御医学研究所分子医科学分野
  • URL: http://www.bioreg.kyushu-u.ac.jp/saibou/index.html
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/saibou/index.html
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/saibou/index.html
• [Patent(Industrial Property Rights)] タンパク質の定量方法 (2009)
  • Inventor(s): 中山敬一・松本雅記
  • Industrial Property Rights Holder: 国立大学法人九州大学
  • Filing Date: 2009-07-17