Molecular mechanism for secretory granule dynamics and exocytosis

• Project/Area Number: 19770159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Gunma University
• Principal Investigator: TORII Seiji Gunma University, 生体調節研究所, 助教 (40312904)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 細胞構造・機能 / 分泌 / インスリン / 分泌顆粒 / 細胞増殖 / 糖尿病 / 開口放出 / 細胞膜

Research Abstract

フォグリンは分泌顆粒に局在する膜蛋白質で、動態観察に有用なマーカーである。本研究では、低糖環境で誘導されるインスリン分解機構について、フォグリン融合蛋白質による新しい顆粒分解検出法を開発した。また同時に、新しい細胞死誘導経路を明らかにした。さらには、遺伝子ノックダウン解析によりフォグリンの膵β細胞における生理機能を見出した。興味深いことに、フォグリンは内分泌ホルモンのオートクライン作用を特異的に制御する初めての蛋白質である。

Research Products

• [Journal Article] Elucidation of Rab27 Recruitment by Its Effectors : Structure, of Rab27a Bound to Exophilin4/S1p2-a (2009)
  • Author(s): Chavas LM, et.al.
  • Journal Title: Structure 16 Pages: 1468-1477
  • Peer Reviewed
• [Journal Article] Gene silencing of phogrin unveils its essential role in glucose-responsive pancreatic beta-cell growth (2009)
  • Author(s): Torii S, et.al.
  • Journal Title: Diabetes 58 Pages: 682-692
  • Peer Reviewed
• [Journal Article] Gene silencing of phogrin unveils its essential role in glucose-responsive pancreatic beta-cell growth (2008)
  • Author(s): Torii S, Saito N, Kawano A, Hou N, Ueki K, Kulkarni RN, Takeuchi T
  • Journal Title: Diabetes
  • Peer Reviewed
• [Journal Article] Elucidation of Rab27 Recruitment by Its Effectors: Structure of Rab27a Bound to Exophilin4/Slp2-a (2008)
  • Author(s): Chavas LM, Ihara K, Kawasaki M, Torii S, Uejima T, Kato R, Izumi T, Wakatsuki S
  • Journal Title: Structure 16 Pages: 1468-1477
  • Peer Reviewed
• [Journal Article] Reactive Oxygen Species-mediated Pancreatic {beta}-cell Death is Regulated by Interactions between Stress-Activated Protein Kinases, p38 and JNK, and MAP Kinase Phosphatases (2008)
  • Author(s): Hou N, Torii S, Saito N, Hosaka M, Takeuchi T
  • Journal Title: Endocrinology 149 Pages: 1654-1665
  • Peer Reviewed
• [Journal Article] Reactive Oxygen Species-mediated Pancreatic {beta}-cell Death is Regulated by Interactions between Stress-Activated Protein Kinases, p38 and JNK, and MAP Kinase Phosphatases (2008)
  • Author(s): Hou N, et.al.
  • Journal Title: Endocrinology 149 Pages: 1654-1665
  • Peer Reviewed
• [Journal Article] ROS-mediated pancreatic b-cell death is regulated by interactions between SAP kinases, p38 and JNK. and MAP kinase phosphatases. (2008)
  • Author(s): Hou N, et. al.
  • Journal Title: Endocrinology 149 Pages: 1654-1665
  • Peer Reviewed
• [Journal Article] Structure of the small GTPase Rab27b shows an unexpected swapped dimer (2007)
  • Author(s): Chavas LM, Torii S, Kamikubo H, Kawasaki M, Ihara K, Kato R, Kataoka M, Izumi T, Wakatsuki S
  • Journal Title: Acta Crystallogr D Biol Crystallogr 63(Pt 7) Pages: 769-779
  • Peer Reviewed
• [Journal Article] Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique Ca2+-inhibitory phospholipid- binding activity of the C2A domain (2007)
  • Author(s): Yu M, Kasai K, Nagashima K, Torii S, Yokota-Hashimoto H, Okamoto K, Takeuchi T, Gomi H, Izumi
  • Journal Title: Mol Biol Cell 18 Pages: 688-696
  • Peer Reviewed
• [Journal Article] Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique Ca2+-inhibitory phospholipid-binding activity of the C2A domain. (2007)
  • Author(s): Yu M, et. al.
  • Journal Title: Mol Biol Cell 18 Pages: 688-696
  • Peer Reviewed
• [Journal Article] Structure of the small GTPase Rab27b shows an unexpected swapped dimer. (2007)
  • Author(s): Chavas LM, et. al.
  • Journal Title: Acta Crystallogr D Biol Crystallogr 63 Pages: 769-779
  • Peer Reviewed
• [Presentation] A secretory granule-resident protein- tyrosine phosphatase phogrin regulates autocrine insulin signaling in pancreatic b-cells (2008)
  • Author(s): Seiji Torii
  • Organizer: 第8回国際プロテインホスファターゼカンファレンス
  • Place of Presentation: 前橋
  • Year and Date: 2008-11-14
• [Presentation] A secretory granule-resident protein-tyrosine phosphatase phogrin regulates autocrine insulin signaling in pancreatic b-cells (2008)
  • Author(s): Seiji Torii
  • Organizer: 国際プロテインホスファターゼカンファレンス
  • Place of Presentation: 前橋
  • Year and Date: 2008-11-14
• [Presentation] 分泌顆粒膜タンパク質Phogrinはグルコース応答性の膵ベータ細胞増殖を制御する (2008)
  • Author(s): 鳥居征司、斎藤直也、竹内利行
  • Organizer: 第60回日本細胞生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-01
• [Presentation] 分泌顆粒膜タンパク質Phogrinはグルコース応答性の膵べータ細胞増殖を制御する (2008)
  • Author(s): 鳥居征司, 他2名
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-01
• [Presentation] 分泌顆粒膜タンパク質フォグリンは膵β細胞の増殖を制御する (2008)
  • Author(s): 鳥居征司、斎藤直也、竹内利行
  • Organizer: 第51回日本糖尿病学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-23
• [Presentation] 分泌顆粒膜タンパク質フォグリンは膵β細胞の増殖を制御する (2008)
  • Author(s): 烏居征司, 他2名
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-23