Analysis of the conformational transitions and functional modifications in membrane proteins

2013 Fiscal Year Final Research Report

• Project Area: Integrative understanding of biological processes mediated by transient macromolecular complexes; New technology for visualizing physiologically metastable states.
• Project/Area Number: 21121007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Osaka University
• Principal Investigator: HAYASAKA Haruko 大阪大学, 医学(系)研究科(研究院), 助教 (70379246)
• Co-Investigator(Kenkyū-buntansha): BAI Zongbin 大阪大学, 免疫学フロンティア研究センター, 特任助教 (10512840)
• Co-Investigator(Renkei-kenkyūsha): MIYASAKA Masayuki 大阪大学, 医学系研究科, 教授 (50064613)
• Project Period (FY): 2009-07-23 – 2014-03-31
• Keywords: ケモカイン / 細胞運動 / 接着分子

Research Abstract

In various cancer cells, the expression of adhesion molecules and chemokine receptor shows a positive correlation with the metastatic potential, suggesting a possible involvement of those molecules in cancer metastasis. CD44 plays a role in cell adhesion by binding to its ligand hyaluronate. Chemokines are critical regulators of cell migration in the context of effective and appropriate immune responses, inflammation, angiogenesis and tumor progression. In this research project, we found that the transition of CD44 molecular structure by ligand binding is possibly involved in the CD44-mediated tumor progression. We also found that the dynamics of chemokine receptor localization on the plasma membrane are important for their function in cell migration.

Research Products

• [Journal Article] Dynamic changes in endothelial cell adhesion molecule nepmucin/CD300LG expression under physiological and pathological conditions (2013)
  • Author(s): Umemoto, E., Takeda, A., Jin, S., Luo, Z., Nakahogi, N., Hayasaka, H., Lee, CM., Tanaka, T., and Miyasaka, M
  • Journal Title: PLoS ONE Volume: 8 Pages: e83681
• [Journal Article] FAK-related nonkinase is a multifunctional negative regulator of pulmonary fibrosis (2013)
  • Author(s): Ding, Q., Cai, G-Q., Hu, M., Yang, Y., Zheng, A., Tang, Q., Gladson, CL., Hayasaka, H.,Wu, H., You, Z., Southern, BD., Grove, LM., Rahaman, SO., Fang,H., and Olman, MA
  • Journal Title: Am. J. Pathol Volume: 182 Pages: 1572-1584
• [Journal Article] Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis (2013)
  • Author(s): Bai, Z., Cai, L., Umemoto, E., Takeda, A., Tohya, K., Komai, Y., Veeraveedu, PT., Hata, E., Sugiura, Y., Kubo, A., Suematsu, M., Hayasaka, H., Okudaira, S., Aoki, J., Tanaka T., Albers, HMHG., Ovaa, H., and Miyasaka, M
  • Journal Title: J. Immunol Volume: 190 Pages: 2036-2048
• [Journal Article] Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-mediated signaling (2012)
  • Author(s): Umemoto, E., Otani, K Ikeno, T., Verjan Garcia N, Hayasaka, H., Bai, Z., Jang MH., Tanaka T., Ueda, K., and Miyasaka, M
  • Journal Title: J. Immunol Volume: 189 Pages: 191-199
• [Journal Article] Novel regulators of lymphocyte trafficking across high endothelial venules (2011)
  • Author(s): Umemoto, E., Hayasaka, H., Bai, Z., Cai, L., Yonekura, S., Peng, X., Takeda, A., Tohya, K., Miyasaka, M
  • Journal Title: Crit. Rev. Immunol Volume: 31 Pages: 147-169
• [Journal Article] Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking (2010)
  • Author(s): Hayasaka, H., Taniguchi, K., Fukai, S. and Miyasaka, M
  • Journal Title: Cancer Sci Volume: 101 Pages: 2302-2308
• [Journal Article] Two-state conformations in the hyaluronan-binding domain regulate CD44 adhesiveness under flow condition (2010)
  • Author(s): Ogino, S., Nishida, N., Umemoto, R., Suzuki, M., Takeda, M., Terasawa, H., Kitayama, J., Matsumoto, M., Hayasaka, H., Miyasaka, M., and Shimada, I
  • Journal Title: Structure Volume: 18 Pages: 649-656
• [Journal Article] CXCL12 promotes CCR7-dependent naïve T cell trafficking to lymph nodes and Peyer's patches (2009)
  • Author(s): Bai, Z, Hayasaka, H (co-first authors), Kobayashi, M, Li,W, Guo, Z, Jang, MH, Kondo, A, Choi, BI, Iwakura, Y, and Miyasaka, M
  • Journal Title: J. Immunol Volume: 182 Pages: 1287-1295
• [Presentation] Chemokine receptor oligomerization : a potential mechanism for regulating lymphocyte and cancer cell migration (2013)
  • Author(s): Haruko Hayasaka, Daichi Kobayashi, Masayuki Miyasaka
  • Organizer: 第51回日本生物物理学会シンポジウム
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2013-10-29
• [Presentation] The HIV-1 gp120/CXCR4 interaction promotes CCR7-dependent CD4 T cell trafficking into lymph nodes (2012)
  • Author(s): Hayasaka H, Yoshimura H, Kobayashi D, Nakayama EE, Shioda T, Bai Z, Miyasaka M
  • Organizer: Keystone Symposia
  • Place of Presentation: (Poster発表)
  • Year and Date: 20120000
• [Presentation] 白血球、癌細胞の生体内動態調節とケモカイン協働作用 (2011)
  • Author(s): 早坂 晴子
  • Organizer: 新学術領域研究「過渡的複合体」公開シンポジウム
  • Place of Presentation: 東京大学薬学部講堂
  • Year and Date: 2011-07-21
• [Presentation] The effects of HIV-1 gp120 on CCR7 ligand-induced human CD4 T cell trafficking (2010)
  • Author(s): Hayasaka H, Yoshimura H, Nakayama EE, Shioda T, Bai Z, Miyasaka M
  • Organizer: 第14回 国際免疫学会
  • Place of Presentation: (口頭発表)
  • Year and Date: 20100000
• [Presentation] ケモカインレセプターの準安定状態と細胞動態 (2010)
  • Author(s): 早坂 晴子、吉村 洋美、白 忠彬、宮坂 昌之
  • Organizer: 第10回日本蛋白質科学会年会 企画ワークショップ
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2010-06-16