Regulation of immune dynamics by Rap1-RAPL-Mst1 signaling

• Project/Area Number: 21570207
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kwansei Gakuin University
• Principal Investigator: KATAGIRI Koko 関西学院大学, 理工学部, 教授 (00322157)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Rap1 / RAPL / adhesion / autoimmunity / p27 / インテグリン / 遊走 / 接着 / 小胞輸送 / Mst1 / GTPase / ケモカイン / リン酸化 / 低分子G蛋白質

Research Abstract

RAPL, Rap1 binding protein, plays crucial roles in Rap1-dependent lymphocyte adhesion and migration. RAPL-deficient mice experienced age-related lupus-like glomerulonephritis and developed B cell lymphomas. RAPL promoted the nuclear localization of p27, cdk2 inhibitor, and prevented the hyperproliferation of both T and B lymphocytes induced by the crosslinking with the antibody to antigen receptors. These data demonstrated that lymphocyte adhesion and proliferation were coordinately regulated by RAPL, and the deficiency of such molecule solely led to the development of lymphoproliferative diseases.

Research Products

• [Journal Article] Rap1 and integrin inside-out signaling (2012)
  • Author(s): Katagiri K
  • Journal Title: Methods Mol.Biol. Volume: 757 Pages: 279-296
• [Journal Article] Deficiency of Rap1-GTP binding protein RAPL causes lymphoproliferative disorders through the mislocalization of cyclin-dependent kinase inhibitor p27^<kip1> (2011)
  • Author(s): Katagiri K, Ueda Y, Tomiyama T, Yasuda K, Toda Y, Ikehara S, Nakayama I. K and Kinashi T
  • Journal Title: Immunity Volume: 34 Pages: 24-38
  • Peer Reviewed
• [Journal Article] Deficiency of Rap1-GTP binding protein RAPL causes lymphoproliferative disorders through the mislocalization of cyclin-dependent kinase inhibitor p27^<kip1>. (2011)
  • Author(s): Katagiri K.
  • Journal Title: Immunity Volume: 34 Pages: 24-38
  • Peer Reviewed
• [Journal Article] Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and-independent manners (2010)
  • Author(s): Katagiri K, Ebisuno Y, Katakai T, Ueda Y, Nemoto T, Inada H, Nabekura J, Okada T, Kannagi R, Tanaka T, Miyasaka M, Hogg N, Kinashi T
  • Journal Title: Blood Volume: 115 Pages: 804-14
  • Peer Reviewed
• [Journal Article] Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and-independent manners. (2010)
  • Author(s): Katagiri, K
  • Journal Title: Blood 115 Pages: 804-14
  • Peer Reviewed
• [Journal Article] Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes (2009)
  • Author(s): Katagiri K, Katakai T, Ebisuno Y, Ueda Y, Okada T, Kinashi T
  • Journal Title: EMBO J Volume: 28 Pages: 1319-31
  • Peer Reviewed
• [Presentation] Deficiency of RAPL causes lymphoproliferative disorders through the mislocalization of p2^<7kip1> (2012)
  • Author(s): 片桐晃子
  • Organizer: 40^<th> keystone symposia
  • Place of Presentation: Breckenridge, USA
  • Year and Date: 2012-01-10
• [Presentation] Lymhpocyte arrest under shear flow (2011)
  • Author(s): 石原沙耶花、木梨達雄、片桐晃子
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉・日本
  • Year and Date: 2011-11-29
• [Presentation] Rab13 is critical for LFA-1 clustering required for lymphocyte migration (2011)
  • Author(s): 金みんす、木梨達雄、片桐晃子
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-29
• [Presentation] Lymhpocyte arrest under shear flow (2011)
  • Author(s): 石原沙耶花
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-11-29
• [Presentation] Rab13 is critical for LFA-1 clustering required for lymphocyte migration (2011)
  • Author(s): 金みんす
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-11-29
• [Presentation] Deficiency of RAPL causes lymphoproliferative disorders through the mislocalization of p27^<kip1> (2011)
  • Author(s): Katagiri K., et. al.
  • Organizer: 2^<nd> RASSF meeting
  • Place of Presentation: Oxford, UK
  • Year and Date: 2011-07-14
• [Presentation] Deficiency of RAPL causes lymphoproliferative disorders through the mislocalization of p2^<7kip1> (2011)
  • Author(s): 片桐晃子
  • Organizer: 2^<nd> RASSF meeting
  • Place of Presentation: Oxford, UK
  • Year and Date: 2011-07-14
• [Presentation] Deficiency of Rap1 binding protein RAPL causes lymphoproliferative disorders through the mislocalization of p27^<kip1> (2011)
  • Author(s): Katagiri K., et. al.
  • Organizer: 40^<th> keystone symposia
  • Place of Presentation: Breckenridge, USA
  • Year and Date: 2011-01-10
• [Presentation] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in RAPL-dependent and-independent manners (2010)
  • Author(s): Ishihara S., Katagiri, K., et. al.
  • Organizer: 14^<th> international congress of immunology
  • Place of Presentation: 神戸・日本
  • Year and Date: 2010-08-23
• [Presentation] Mst1 controls lymphocyte trafficking and motility within lymph nodes (2010)
  • Author(s): Kim, M., Katagiri K., et. al.
  • Organizer: 14^<th> international congress of immunology
  • Place of Presentation: 神戸・日本
  • Year and Date: 2010-08-23
• [Presentation] Regulation of lymphocyte polarization and motility by Rab proteins (2009)
  • Author(s): 吉田行輝、木梨達雄、片桐晃子
  • Organizer: 第38回日本免疫学会総会・学術会議
  • Place of Presentation: 大阪・日本
  • Year and Date: 2009-12-01
• [Presentation] Rap1 controls lymphocyte adhesion cascades (2009)
  • Author(s): 河田美穂、片桐晃子、木梨達雄
  • Organizer: 第38回日本免疫学会総会・学術会議
  • Place of Presentation: 大阪・日本
  • Year and Date: 2009-12-01
• [Presentation] Regulation of lymphocyte polarization and motility by Rab proteins (2009)
  • Author(s): 吉田行輝
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-01