Spatio-temporal analysis of DOCK180 during dorsal ruffle formation

2013 Fiscal Year Final Research Report

• Project/Area Number: 24770127
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Kyushu University
• Principal Investigator: SANEMATSU FUMIYUKI 九州大学, 生体防御医学研究所, 助教 (80381094)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ラッフル膜形成 / Rac活性化分子 / DOCK180

Research Abstract

Activation of receptor tyrosine kinases leads to the formation of two different types of plasma membrane structures: peripheral ruffles and dorsal ruffles. Although the formation of both ruffle types requires activation of the small GTPase Rac, the difference in kinetics suggests that a distinct regulatory mechanism operates for their ruffle formation. DOCK1(DOCK180) and DOCK5 are atypical Rac activators and are both expressed in mouse embryonic fibroblasts (MEFs). We found that DOCK1 deficiency alone impaired dorsal ruffle formation in MEFs. DOCK1 bound to phosphatidic acid (PA) through the C-terminal polybasic amino acid cluster and was localized to dorsal ruffles. In addition, we show that phospholipase D, an enzyme that catalyzes PA synthesis, is required for PDGF-induced dorsal, but not peripheral, ruffle formation. These results indicate that the phospholipase D-PA axis selectively controls dorsal ruffle formation by regulating DOCK1 localization.

Research Products

• [Journal Article] The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation (2013)
  • Author(s): Sakai, Y., Tanaka, Y., Yanagihara, T., Watanabe, M., Duan, X., Terasawa, M., Nishikimi, A., Sanematsu, F., Fukui. Y.
  • Journal Title: Blood Volume: 122(3) Pages: 386-93
  • Peer Reviewed
• [Journal Article] Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation (2013)
  • Author(s): Sanematsu, F., Nishikimi, A., Watanabe, M., Hongu, T., Tanaka, Y., Kanaho, Y., Côté, J.F., Fukui, Y.
  • Journal Title: J Biol. Chem. Volume: 288(12) Pages: 8092-100
  • Peer Reviewed
• [Journal Article] Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration (2012)
  • Author(s): Terasawa, M., Uruno, T., Mori, S., Kukimoto-Niino, M., Nishikimi, A., Sanematsu, F., Tanaka, Y., Yokoyama, S., Fukui, Y.
  • Journal Title: PLoS One Volume: 7(9) Pages: e46277
  • Peer Reviewed
• [Journal Article] 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(4) Pages: 488-97
  • Peer Reviewed
• [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses (2012)
  • Author(s): Harada, 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(19) Pages: 4451-61
  • Peer Reviewed
• [Presentation] Dorsal ruffle形成時におけるDOCK1の役割とその制御 (2012)
  • Author(s): 實松史幸, 錦見昭彦, 渡邉真裕紀, 本宮綱記, 田中芳彦, 金保安則, Jean-Francois Cote, 福井宣規
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/iden/