Roles of scaffolding proteins in the formation of transportsome

2009 Fiscal Year Final Research Report

• Project/Area Number: 17081008
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HATA Yutaka Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (80313237)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA Kentaro 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (70451929) ; IKEDA Misunobu 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (00451930)
• Project Period (FY): 2005 – 2009
• Keywords: トランスポーター / チャネル / 細胞接着 / 細胞極性 / 細胞死 / シグナル伝達

Research Abstract

Cell junctions are important not only for cell adhesion but also for signal transduction. Thereby, we focused on S-SCAM(MAGI2), MAGI1, and LNX1, all of which are localized at cell junctions. We revealed the roles of S-SCAM at excitatory and inhibitory synapses, of MAGI1 at kidney diaphragm, and of LNX1 in the endocytosis of a cell adhesion molecule named JAM4 during the epithelial and mesenchymal transition. We also identified RASSF6 as a new MAGI1-binding partner, which mediates apoptosis. A protein kinase named MST2 functions as a scaffold to assemble a complex including RASSF6 and blocks RASSF6-induced apoptosis. Once MST2 is activated, RASSF6 is released from the complex. This finding implies that MST2 is a dynamic scaffold to directly regulate protein interactions.

Research Products

• [Journal Article] Filamin associates with stress signaling kinases MKK7 and MKK4 and regulates JNK activation. (2010)
  • Author(s): Nakagawa K, Sugahara M, Yamasaki T, Kajiho H, Takahashi S, Hirayama J, Minami Y, Ohta Y, Watanabe T, Hata Y, Katada T, Nishina H.
  • Journal Title: Biochem. J. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Roles of mammalian sterile 20-like kinase 2-dependent phosphorylations of Mps one binder 1B in the activation of nuclear Dbf2-related kinases. (2009)
  • Author(s): Bao Y, Sumita K, Kudo T, Withanage K, Nakagawa K, Ikeda M, Ohno K, Wang Y, Hata Y.
  • Journal Title: Genes Cells 14巻12号 Pages: 1369-1381
  • Peer Reviewed
• [Journal Article] Hippo pathway-dependent and -independent roles of RASSF6. (2009)
  • Author(s): Ikeda M, Kawata A, Nishikawa M, Tateishi Y, Yamaguchi M, Nakagawa K, Hirabayashi S, Bao Y, Hidaka S, Hirata Y, Hata Y.
  • Journal Title: Sci Signal. 2巻90号 Pages: ra59
  • Peer Reviewed
• [Journal Article] Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1. (2008)
  • Author(s): Hirabayashi S, Nakagawa K, Sumita K, Hidaka S, Kawai T, Ikeda M, Kawata A, Ohno K, Hata Y.
  • Journal Title: Oncogene 27巻31号 Pages: 4281-4292
  • Peer Reviewed
• [Journal Article] Co-localization of a novel transcriptional repressor simiRP58 with RP58. (2008)
  • Author(s): Takahashi A, Hirai S, Ohtaka-Maruyama C, Miwa A, Hata Y, Okabe S, Okado H.
  • Journal Title: Biochem. Biophys. Res. Commun. 368巻 Pages: 637-642
  • Peer Reviewed
• [Journal Article] S-SCAMalpha is a scaffold to mediate NMDA receptor-dependent RhoA activation in dendrites. (2007)
  • Author(s): Iida J, Ishizaki H, Okamoto-Tanaka M, Kawata A, Sumita K, Ohgake S, Sato Y, Yorifuji H, Nukina, N, Ohashi K, Mizuno K, Tsutsumi T, Mizoguchi A, Miyoshi J, Takai Y, Hata Y.
  • Journal Title: Mol. Cell. Biol. 27巻12号 Pages: 4388-4405
  • Peer Reviewed
• [Journal Article] Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. (2007)
  • Author(s): Ikeda M, Hirabayashi S, Fujiwara N, Mori H, Kawata A, Iida J, Bao Y, Sato Y, Iida T, Sugimura H, Hata Y.
  • Journal Title: Exp. Cell Res. 313巻7号 Pages: 1484-1495
  • Peer Reviewed
• [Journal Article] S-SCAM/MAGI-2 is associated with cell adhesion molecules at inhibitory synapses at rat hippocampal neurons. (2007)
  • Author(s): Sumita K, Sato Y, Iida J, Kawata A, Hamano M, Hirabayashi S, Ohno K, Peles E, Hata Y.
  • Journal Title: J. Neurochem. 100巻1号 Pages: 154-166
  • Peer Reviewed
• [Journal Article] Monoclonal antibody 7F9 recognizes rat protein homologous to human carboxypeptidase-M in rat developing and adult lung. (2007)
  • Author(s): Fujiwara N, Ikeda M, Hirabayashi S, Mori H, Shirasawa M, Kansaku A, Sunamori M, Hata Y.
  • Journal Title: Respirology 12巻1号 Pages: 54-62
  • Peer Reviewed
• [Journal Article] CTX family cell adhesion molecule, JAM4, expresses in stem cell- and progenitor cell populations of both male germ cell and hematopoietic cell lineages. (2006)
  • Author(s): Nagamatsu G, Ohmura M, Mizukami T, Hamaguchi I, Hirabayashi S, Yoshida S, Hata Y, Suda T, Ohbo K.
  • Journal Title: Mol. Cell. Biol. 24巻 Pages: 8498-8506
  • Peer Reviewed
• [Journal Article] Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4. (2006)
  • Author(s): Kansaku A, Hirabayashi S, Mori H, Fujiwara N, Kawata A, Ikeda M, Rokukawa C, Kurihara H, Hata Y.
  • Journal Title: Oncogene 25巻37号 Pages: 5071-5084
  • Peer Reviewed
• [Journal Article] CIN85 is localized at synapses and forms a complex with S-SCAM via Dendrin. (2006)
  • Author(s): Kawata A, Iida J, Ikeda M, Sato Y, Mori H, Kansaku A, Sumita K, Fujiwara N, Rokukawa C, Hamano M, Hirabayashi S, Hata Y.
  • Journal Title: J. Biochem. 139巻5号 Pages: 931-939
  • Peer Reviewed
• [Journal Article] Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. (2006)
  • Author(s): Uchida T, Shirasawa M, Ware LB, Kojima K, Hata Y, Makita K, Mednick G, Matthay ZA, Matthay MA.
  • Journal Title: Am. J. Respir. Crit. Care Med. 173巻9号 Pages: 1008-1015
  • Peer Reviewed
• [Journal Article] MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin. (2005)
  • Author(s): Hirabayashi S, Mori H, Kansaku A, Sakai H, Shimizu F, Kawachi H, Hata Y.
  • Journal Title: Lab. Invest. 85巻12号 Pages: 1528-1543
  • Peer Reviewed
• [Presentation] Hippo pathway-dependent and -independent roles of RASSF6, 細胞死・細胞増殖制御を司る新しいシグナル伝達系Hippo pathway (2009)
  • Author(s): 池田光伸、畑裕
  • Organizer: 第82回日本生化学会大会 シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Dual roles of RASSF6 in mammalian Hippo pathway. (2009)
  • Author(s): Yutaka Hata
  • Place of Presentation: Rome, Italy
  • Year and Date: 2009-04-22
• [Presentation] The regulatory mechanism of RASSF6-mediated cell death. (2009)
  • Author(s): Yutaka Hata
  • Organizer: First International RASSF Symposium.
  • Place of Presentation: Banff, Canada.
  • Year and Date: 2009-02-06
• [Presentation] アダプター分子MOB1のリン酸化がNuclear Dbf2-relatedキナーゼファミリーの選択的な活性化を制御する (2008)
  • Author(s): 中川健太郎、包義君、工藤琢己、壽美田一貴、畑裕
  • Organizer: 回日本分子生物学会年会、第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20081210-20081211
• [Presentation] RASSF3による細胞死誘導の解析 (2007)
  • Author(s): 掛真太郎、中川健太郎、池田光伸、壽美田一貴、畑裕
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] ke kinase (MST) 2の相互作用とその機能の解析 (2007)
  • Author(s): 川田現、池田光伸、飯田純子、包義君、中川健太郎、平林享、日高志穂、畑裕
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] MST2とMOB1によるNuclear Dbf2-related kinase 1の活性化機構とその生理的意義の検討 (2007)
  • Author(s): 日高志穂、中川健太郎、平林享、壽美田一貴、川田現、河合朋光、畑裕
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Linkage of membrane proteins to the actin cytoskeleton by members of the MAGI family of junction scaffold proteins. (2006)
  • Author(s): Yutaka Hata
  • Organizer: Max-Planck-Institut fur Experimentelle Medizin Abteilung Molekulare Neurobiologie
  • Place of Presentation: Goettingen, Germany
  • Year and Date: 2006-12-13
• [Presentation] 新規RASSFファミリー分子RASSF6の細胞増殖制御機構の解析 (2006)
  • Author(s): 平林享、藤原直之、畑裕
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-28
• [Presentation] シナプス接着分子neuroliginを裏打ちする足場蛋白S-SCAM/MAGI-2が司る蛋白相互作用 (2006)
  • Author(s): 畑裕、飯田純子、壽美田一貴、川田現、佐藤勇次
  • Organizer: 第28回日本生物学的精神医学会、第36回日本神経精神薬理学会、第49回日本神経化学会大会合同年会NC理事会企画オープンシンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-09-14
• [Presentation] 抑制性シナプスにおけるS-SCAMの解析 (2006)
  • Author(s): 壽美田一貴、佐藤勇次、川田現、飯田純子、大野喜久郎、畑裕
  • Organizer: 第29回日本神経科学会大会
  • Place of Presentation: 京都
  • Year and Date: 2006-07-19
• [Presentation] Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4 (2006)
  • Author(s): 平林享、神作愛、池田光伸、川田現、藤原直之、森弘樹、六川千秋、栗原秀剛、畑裕
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress in conjunction with 79th Annual Meeting of the Japanese Biochemical Society and 29th Annual Meeting of the Molecular Biology Society for Japan
  • Place of Presentation: 京都
  • Year and Date: 2006-06-20
• [Presentation] 腎臓糸球体スリット膜を支える分子複合体の解析, 生体膜分子複合体の分子構築と生理機能 (2005)
  • Author(s): 平林享、神作愛、畑裕
  • Organizer: 生理学研究所研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2005-07-19
• [Presentation] 足場蛋白S-SCAMによるシナプス分子複合体の形成, 分子複合体と神経シナプス機能 (2005)
  • Author(s): 飯田純子、畑裕
  • Organizer: 生理学研究所研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2005-06-23
• [Book] proteins: tight junction proteins that belong to the immunoglobulin superfamily.(edited by Gonzalez-Mariscal, Tight Junctions) (2006)
  • Author(s): Hirabayashi S, Hata Y. JAM family
  • Total Pages: 43-53
  • Publisher: L. Landes Biosciences, Springer