Spatiotemporal regulation of Mst1 by RAPL is critical for lymphocyte polarity and adhesion

• Project/Area Number: 17570159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kansai Medical University
• Principal Investigator: KATAGIRI Koko Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00322157)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Integrin / cell adhesion / cell migration / cell polarity / RAPL / Rap1 / STK / TCR / chemokine / LFA-1 / ICAM-1 / activation

Research Abstract

RAPL, a Rap1-binding protein is required for efficient immune cell trafficking. Here, we identify mammalian Ste20-like kinase Mst1 as a critical effector of RAPL. RAPL regulates the localization and kinase activity of Mst1. MST1 knockdown demonstrates its requirement for the induction of both a polarized morphology and LFA-1 clustering and adhesion triggered by chemokines and TCR ligation. RAPL and Mst1 localized to vesicular compartments and dynamically translocated with LFA-1 to the leading edge by Rap1 activation, suggesting the regulatory role of RAPL-Mst1 complex in intracellular transport of LFA-1. Our study reveals a novel function for Mst1, relaying the Rap1-RAPL signal to produce the cell polarity and adhesion of lymphocytes.

Research Products

• [Journal Article] The M-Ras-RA-GEF-2Rap1 pathway mediates tumor-necrosis factor-alpha-dependent regulation of integrin activation in splenocytes. (2007)
  • Author(s): Yoshikawa, Y., Satoh, T., Tamura, T., et al.
  • Journal Title: Mol.Biol. Cell (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The M-Ras-RA-GEF-2Rap 1 pathway mediates tumor-necrosis factor-alpha-dependent regulation of integrin activation in splenocytes. (2007)
  • Author(s): Yoshikawa, Y, Satoh, T., Tamura, T., Wei, P., Bilasy, SE., Edamatsu, H., Aiba, A, Katagiri, K., Kinashi, T., Nakao, K., Kataoka, T.
  • Journal Title: Mol.Biol.Cell (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Spatiotemporal regulation of the Kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. (2006)
  • Author(s): Katagiri, K., Imamura, M., Kinashi, T.
  • Journal Title: Immunol. 7 Pages: 919-927
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Spatiotemporal regulation of the Kinase Mstl by binding protein RAPL is critical for lymphocyte polarity and adhesion. (2006)
  • Author(s): Katagiri, K., Imamura, M., Kinashi, T.
  • Journal Title: Nat.Immunol. 7 Pages: 919-927
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Spatiotemporal regulation of the Kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. (2006)
  • Author(s): Katagiri, K., Imamura, M., Kinashi, T.
  • Journal Title: Nature Immunology 7 Pages: 919-927
• [Journal Article] Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues. (2005)
  • Author(s): Kinashi, T., Katagiri, K.
  • Journal Title: Immunology 116 Pages: 164-171
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CXCL13 is an arrest chemokine for B cells in high endothelial venules. (2005)
  • Author(s): Kanemitsu, N., Ebisuno, Y., Tanaka, T., et al.
  • Journal Title: Blood 106 Pages: 2613-2618
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 免疫細胞の動態制御因子Rap1/RAPL (2005)
  • Author(s): 片桐 晃子, 木梨 達雄
  • Journal Title: 医学のあゆみ 212 Pages: 705-706
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CXCL13 is an arrest chemokine for B cells in high endothelial venules. (2005)
  • Author(s): Kanemitsu, N., Ebisuno, Y., Tanaka, T., Otani, K., Hayasaka, H., Kaisho, T., Akira, S., Katagiri, K., Kinashi, T., Fujita, N., Tsuruo, T., Miyasaka, M.
  • Journal Title: Blood. 106 Pages: 2613-2618
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CXCL13 is an arrest chemokine for B cells in high endothelial venules. (2005)
  • Author(s): Kanemitsu, N., Ebisuno, Y.et al.
  • Journal Title: Blood 106 Pages: 2613-2618
• [Book] 免疫2006 (2006)
  • Author(s): 片桐 晃子, 木梨 達雄, 岸本忠三編
  • Total Pages: 385
  • Publisher: 中山書店
  • Description: 「研究成果報告書概要(和文)」より