Molecular mechanism of neutrophil phagocytosis mediated by DOCK2 and Rac signaling

• Project/Area Number: 22790469
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyushu University
• Principal Investigator: NISHIKIMI Aklhiko 九州大学, 生体防御医学研究所, 助教 (70404019)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 好中球 / 貪食 / 細胞骨格 / 低分子量Gタンパク質 / マクロピノサイトーシス / 感染防御 / 形態変化

Research Abstract

The role of DOCK2 in cytoskeleton rearrangement during neutrophil phagocytosis was investigated. It was found that DOCK2 plays an important role in phagocytosis and macropinocytosis. Real time imaging analysis has shown that DOCK2 accumulated around forming phagosome. I also examined the role of other CDM family proteins in neutrophil phagocytosis. However, these molecules had less effect on neutrophil phagocytosis than DOCK2.

Research Products

• [Journal Article] Fukui, Y. DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses (2012)
  • Author(s): Y., Tanaka, Y., Terasawa, M., Pieczyk, M., Habiro, K., Katakai, T., Hanawa-Suetsugu, K., Kukimoto-Niino, M., Nishizaki, T., Shirouzu, M., Duan, X., Uruno, T., Nishikimi, A., Sanematsu, F., Yokoyama, S., Stein, J. V., Kinashi, T., Fukui, Y.
  • Journal Title: Blood Volume: 119 Pages: 4451-4461
  • Peer Reviewed
• [Journal Article] Fukui, Y. Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2 (2012)
  • Author(s): Nishikimi A., Uruno, T., Duan, X., Cao, Q., Okamura, Y., Saitoh, T., Saito, N., Sakaoka, S., Du, Y., Suenaga, A., Kukimoto-Niino, M., Miyano, K., Gotoh, K., Okabe, T., Sanematsu, F., Tanaka, Y., Sumimoto, H., Honma, T., Yokoyama, S., Nagano, T., Kohda, D., Kanai, M., Fukui, Y.
  • Journal Title: Chem. Biol Volume: 19 Pages: 488-497
  • Peer Reviewed
• [Journal Article] Structural basis for mutual relief of DOCK2 and ELMO1 from their autoinhibited forms for Rac activation in lymphocyte chemotaxis (2012)
  • Author(s): Hanawa-Suetsugu, K., Kukimoto-Niino, M., Mishima-Tsumagari, C., Akasaka, R., Ohsawa, N., Sekine, S., Ito, T., Tochio, N., Koshiba, S., Kigawa, T., Terada, T., Shirouzu, M., Nishikimi, A., Uruno, T., Katakai, T., Kinashi, T., Kohda, D., Fukui, Y., Yokoyama
  • Journal Title: Proc. Natl. Acad. Sci.USA Volume: 109 Pages: 3305-3310
  • Peer Reviewed
• [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migrataon during immune responses (2012)
  • Author(s): Yosuke Harada, Yoshihiko Tanaka, Masao Terasawa, Markus Pieczyk, Katsuyoshi Habiro, Tomoya Katakai, Kyoko Hanawa-Suetsugu, Mutsuko Kukimoto-Niino, Tomoko Nishizaki, Mikako Shirouzu, Xuefeng Duan, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Shigeyuki Yokoyama, Jens V.Stein, Tatsuo Kinashi, Yoshinori Fukui
  • Journal Title: Blood Volume: (In press) Issue: 19 Pages: 4451-4461
  • DOI: 10.1182/blood-2012-01-407098
  • Peer Reviewed
• [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2 (2012)
  • Author(s): Nishikimi A, et al
  • Journal Title: Chem.Biol. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms. (2012)
  • Author(s): Hanawa-Suetsugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinashi T, Kohda D, Fukui Y, Yokoyama S
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Issue: 9 Pages: 3305-3310
  • DOI: 10.1073/pnas.1113512109
  • Peer Reviewed
• [Journal Article] DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. (2010)
  • Author(s): Sanematsu, et al.
  • Journal Title: Circulation Research Volume: 107 Pages: 1102-1105
  • Peer Reviewed
• [Journal Article] Selective of type I INF induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. (2010)
  • Author(s): Gotoh, et al.
  • Journal Title: Journal of Experimental Medicine Volume: 207 Pages: 721-730
  • Peer Reviewed
• [Presentation] 免疫系特異的なRac活性化因子DOCK2を標的とした免疫抑制剤の開発 (2012)
  • Author(s): 錦見昭彦、田中芳彦、福井宣規
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2012-11-27
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/iden/
• [Patent(Industrial Property Rights)] DOCK2によるRac活性化を制御する低分子化合物及びその用途 (2011)
  • Inventor(s): 福井宣規、錦見昭彦、金井求、神田大輔、齋藤貴士
  • Industrial Property Rights Holder: 九州大学、東京大学
  • Filing Date: 2011-05-16
• [Patent(Industrial Property Rights)] DOCK2によるRac活性化を制御する低分子化合物及びその用途 (2011)
  • Inventor(s): 福井宣規, 錦見昭彦, 金井求, 神田大輔, 齋藤貴士
  • Industrial Property Rights Holder: 九州大学, 東京大学
  • Industrial Property Number: 2011-109334
  • Filing Date: 2011-05-16