A study of epidermal morphogenesis regulated by semaphorin signaling

• Project/Area Number: 21370097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Nagoya University
• Principal Investigator: TAKAGI Shin 名古屋大学, 理学研究科, 准教授 (90171420)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2009: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: セマフォリン / 表皮 / 形態形成 / 線虫 / TOR / 器官形成 / 線虫C. elegans / 表皮細胞 / 膜ダイナミクス / 細胞形態 / 遺伝学検索

Research Abstract

The target of rapamycin (TOR) resides in the two functionally distinct complexes TORC1 and TORC2, which are defined by their adaptors Raptor and Rictor, respectively. How the formation of the two TORCs is orchestrated remains unclear. Through our study in C. elegans, we demonstrated the control of TOR partnering by semaphorin-plexin signaling in vivo. In semaphorin and plexin mutants, TOR-Raptor association decreases whereas TOR-Rictor association increases, concomitantly with TORC1 down- and TORC2 up-regulation. Epidermal defects in semaphorin and plexin mutants are suppressed by inhibiting TORC2 or reinforcing TORC1 signaling. Conversely, inhibition of TORC1 signaling phenocopies semaphorin and plexin mutants. Our results indicate that TORC formation is a singularly important step in semaphorin signaling that culminates in diverse outcomes including TORC1-promoted mRNA translation and TORC2-regulated cytoskeletal remodeling.

Research Products

• [Journal Article] セマフォリンシグナルを介した TOR アダプター因子の選択機構 (2012)
  • Author(s): 糠塚 明、 高木 新
  • Journal Title: 実験医学 Volume: 30(3) Pages: 475-478
• [Journal Article] A shift of the TOR adaptor from rictor toward raptor by semaphorin in C. elegans (2011)
  • Author(s): Nukazuka, A., Tamaki, S., Matsumoto, K., Oda, Y., Fujisawa, H., and Takagi, S
  • Journal Title: Nature Commun Volume: 2 Issue: 1 Pages: 484-484
  • DOI: 10.1038/ncomms1495
  • Peer Reviewed
• [Journal Article] 赤外レーザーによる局所的遺伝子発現誘導法 (2010)
  • Author(s): 浦和博子, 他
  • Journal Title: 比較内分泌学 Volume: 138 Pages: 217-221
• [Presentation] Synaptotagmin and Stonin is required for efficient EGL-17/FGF secretion by epidermal cells in C (2012)
  • Author(s): Tanaka Hiroki, Shimojou Masaki, Takagi Shin
  • Organizer: elegans. East asia C. elegans meeting.
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2012-06-28
• [Presentation] Synaptotagmin and Stonin is required for efficient EGL-17/FGF secretion in C. elegans (2012)
  • Author(s): Tanaka Hiroki, Shimojou Masaki, Takagi Shin
  • Organizer: 日本分子生物学会大会
  • Place of Presentation: 神戸国際会議場 (神戸)
  • Year and Date: 2012-05-29
• [Presentation] Synaptotagmin and Stonin is required for efficient EGL-17/FGF secretion in C. elegans (2011)
  • Author(s): Tanaka Hiroki, Shimojou Masaki, Takagi Shin
  • Organizer: 日本分子生物学会大会
  • Place of Presentation: パシフィコ横浜 (横浜)
  • Year and Date: 2011-12-14
• [Presentation] 線虫 C. elegans においてセマフォリンは (2011)
  • Author(s): 糠塚 明、玉木 修作、松本 邦弘、小田洋一、藤澤 肇、 高木 新
  • Organizer: TOR の結合アダプタータンパク質を Rictor から Raptor へシフトする RNA フロンティアミーティング
  • Place of Presentation: 愛知健康プラザ(大府市)
  • Year and Date: 2011-08-31
• [Presentation] セマフォリンによる翻訳制御を介した C. elegans 表皮形態形成の調節 (2011)
  • Author(s): 高木 新
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] Up- and Down-regulation of TOR-Raptor and TOR-Rictor Complexes by Semaphorin in C. elegans. RNA Sciences in Developmental Biology (2010)
  • Author(s): Akira Nukazuka, Mie Chikuma, Toshifumi Inada, Yoichi Oda, Hajime Fujisawa, Shin Takagi.
  • Organizer: The 19th CDB Meeting
  • Place of Presentation: 理研 CDB(神戸)
  • Year and Date: 2010-05-11
• [Presentation] Up- and Down-regulation of TOR-Raptor and TOR-Rictor Complexes by Semaphorin in C.elegans (2010)
  • Author(s): Akira Nukazuka, 他
  • Organizer: RNA Sciences in Developmental Biology, The 19th CDB Meeting
  • Place of Presentation: 神戸理研CDB
  • Year and Date: 2010-05-11
• [Presentation] Up-and Down-regulation of TOR-Raptor and TOR-Rictor Complexes by Semaphorin in C.elegans (2010)
  • Author(s): Akira Nukazuka, 他
  • Organizer: RNA Sciences in Developmental Biology, The 19th CDB Meeting
  • Place of Presentation: 神戸 理研CDB
  • Year and Date: 2010-05-11
• [Presentation] Up- and down-regulation of TOR-Raptor and TOR-Rictor complexes by semaphorin in C. elegans (2009)
  • Author(s): Akira Nukazuka, Mie Chikuma, Toshifumi Inada, Yoichi Oda, Hajime Fujisawa, Shin Takagi.
  • Organizer: 17th International C. elegans meeting
  • Place of Presentation: UCLA (Los Angels USA)
• [Presentation] セマフォリンによる翻訳制御を介したC. elegans表皮形態形成の調節
  • Author(s): 高木 新
  • Organizer: 第84回日本生化学会大会、 シンポジウム
  • Place of Presentation: 京都国際会館 （京都）
  • Invited
• [Presentation] Synaptotagmin and Stonin is required for efficient EGL-17/FGF secretion in C. elegans
  • Author(s): Tanaka Hiroki
  • Organizer: 日本分子生物学会大会
  • Place of Presentation: パシフィコ横浜 （横浜）
• [Remarks]
  • URL: http://www.bio.nagoya-u.ac.jp/~m7home/research/takagi.html
• [Remarks]
  • URL: http://www.nu-research.com/index.php?option=com_content&view=article&id=129:biologysemaphorins-contribute-to-cellular-changes-by-regulating-two-tor-complexes&catid=2:entry&Itemid=3
• [Remarks] 「セマフォリンによる細胞の形の制御機構解明」 名大トピックス No.226 2012年3月15日発行
• [Remarks] 「細胞変形、仕組み解明」 日経産業新聞2011年12月2日
• [Remarks] 「動物細胞の形制御 分子の仕組み解明」日刊工業新聞2011年10月18日 3面
• [Remarks] 「細胞の伸び仕組み解明」中日新聞 朝刊 2011年9月28日 3面
• [Remarks] セマフォリンシグナル経路の研究
  • URL: http://www.bio.nagoya-u.ac.jp/~m7home/research/takagi.html
• [Remarks]
  • URL: http://www.bio.nagoya-u.ac.jp/~m7home/m7_research_takagi.htm