Quality control of insulin granule exocytosis

• Project/Area Number: 24390068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Gunma University
• Principal Investigator: IZUMI Tetsuro 群馬大学, 生体調節研究所, 教授 (00212952)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: インスリン / 分泌顆粒 / 開口放出 / 細胞内膜輸送 / 糖尿病

Outline of Final Research Achievements

We have analyzed the function of multiple Rab27 effector proteins expressed in pancreatic beta cells. As a result, we have identified novel roles of three Rab27 effector proteins in insulin granule exocytosis. First, Noc2 has a role in connecting maturation and exocytosis steps by interacting with both Rab2a and Rab27a. Second, exophilin8 is involved in the transport of granules to cell periphery by binding a novel protein. Third, granuphilin is an exclusive component of the functional and fusion-inhibitory docking machinery of secretory granules. Thus, three kinds of Rab27 effector proteins function in completely different exocytic processes in pancreatic beta cells.

Research Products

• [Journal Article] PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a (2016)
  • Author(s): Yamaoka M, Ando T, Terabayashi T, Okamoto M, Takei M, Nishioka T, Kaibuchi K, Matsunaga K, Ishizaki R, Izumi T, Niki I, Ishizaki T, Kimura T
  • Journal Title: Journal of Cell Science Volume: 129 Issue: 3 Pages: 637-649
  • DOI: 10.1242/jcs.180141
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Granuphilin exclusively mediates functional granule docking to the plasma membrane. (2016)
  • Author(s): Mizuno K, Fujita T, Gomi H, and Izumi T
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 23909-23909
  • DOI: 10.1038/srep23909
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rab27A Regulates Transport of Cell Surface Receptors Modulating Multinucleation and Lysosome Related Organellas in osteoclasts (2015)
  • Author(s): Megumi Shimada-Sugawara,Eiko Sakai,Kuniaki Okamoto,Mitsunori Fukuda,Tetsuro Izumi,Noriaki Yoshida,Takayuki Tsukuba
  • Journal Title: SCIENTIFIC REPORTS Volume: 5 Issue: 1 Pages: 9620-9620
  • DOI: 10.1038/srep09620
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes. (2013)
  • Author(s): Yogosawa S, and Izumi T
  • Journal Title: Adipocyte Volume: 2 Issue: 4 Pages: 246-250
  • DOI: 10.4161/adip.24974
  • Peer Reviewed
• [Journal Article] TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis. (2013)
  • Author(s): Fujimoto Y, Nakagawa Y, Satoh A, Okuda K, Shingyouchi A, Naka A, Matsuzaka T, Iwasaki H, Kobayashi K, Yahagi N, Shimada M, Yatoh S, Suzuki H, Yogosawa S, Izumi T, Sone H, Urayama O, Yamada N, Shimano H
  • Journal Title: Endocrinology Volume: 154 Issue: 10 Pages: 3577-88
  • DOI: 10.1210/en.2013-1203
  • Peer Reviewed / Open Access
• [Journal Article] The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane. (2013)
  • Author(s): Wang H., et al.
  • Journal Title: Mol. Biol. Cell Volume: 24 Pages: 319-330
  • Peer Reviewed
• [Journal Article] Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptor γ and C/EBPa. (2013)
  • Author(s): Yogosawa S., et al.
  • Journal Title: Diabetes Volume: 62 Pages: 115-123
  • Peer Reviewed
• [Journal Article] Adipose cell and lipid turnovers in obesity and insulin resistance. (2012)
  • Author(s): Izumi T
  • Journal Title: Diabetol. Int. Volume: 3 Issue: 4 Pages: 184-186
  • DOI: 10.1007/s13340-012-0092-9
  • NAID: 10030590045
  • Peer Reviewed
• [Presentation] Rab27エフェクターExophilin8ノックアウトマウスのインスリン分泌制御における解析。 (2016)
  • Author(s): 范 福順、松永 耕一、泉 哲郎
  • Organizer: 第30回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: さいたま
  • Year and Date: 2016-03-11
• [Presentation] 膵B細胞におけるエンドサイトーシスの時間的・空間的制御機構の解析。 (2015)
  • Author(s): 山岡 真美、寺林 健、松永 耕一、泉 哲郎、仁木 一郎、石崎 敏理、木村 俊秀
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Novel functions of Rab27 effector proteins in insulin granule exocytosis. (2015)
  • Author(s): Tetsuro Izumi
  • Organizer: The 2015 Gordon Conferences on Pancreatic Diseases
  • Place of Presentation: South Hadley, Massachusetts, USA
  • Year and Date: 2015-07-19
  • Int'l Joint Research / Invited
• [Presentation] Functional cross-talk between Rab27a and Rab2a via their dual effector is required for insulin granule maturation and secretion in pancreatic beta cells. (2015)
  • Author(s): Kohichi Matsunaga, Masato Taoka, Toshiaki Isobe, Tetsuro Izumi
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] Rab27エフェクター蛋白メラノフィリンのインスリン分泌における役割。 (2015)
  • Author(s): 王 昊、奥西 勝秀、泉 哲郎
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-23
• [Presentation] Functional cross-talk between Rab2a and Rab27a through their dual effector is required for insulin granule maturation and secretion in pancreatic beta cells. (2014)
  • Author(s): Kohichi Matsunaga, Masato Taoka, Toshiaki Isobe, and Tetsuro Izumi
  • Organizer: International Symposium on Homeostasis through development, life, and diseases
  • Place of Presentation: Gunma University, Maebashi, Gunma, Japan
  • Year and Date: 2014-11-07
• [Presentation] Rab27Aは破骨細胞の多核化とリソソーム機能を制御する。 (2014)
  • Author(s): 菅原 めぐみ、坂井 詠子、福間 裕、西下 一久、岡元 邦彰、福田 光則、泉 哲郎、吉田 教明、筑波 隆幸
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-10-17
• [Presentation] Exophilin8遺伝子改変マウスを用いたインスリン分泌制御機構の解析。 (2014)
  • Author(s): 范 福順、松永 耕一、泉 哲郎
  • Organizer: 第61回北関東医学会総会
  • Place of Presentation: 群馬大学（群馬県前橋市）
  • Year and Date: 2014-09-26
• [Presentation] Identification of Rab27a-GAP-interacting proteins and its functional analysis in pancreatic beta-cells. (2014)
  • Author(s): M. Yamaoka, T. Ando, M. Okamoto, T. Terabayashi, T. Izumi, I. Niki, T. Ishizaki, and T. Kimura
  • Organizer: 50th Annual meeting of European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-09-18
• [Presentation] The role of Rab27 effector Exophilin8 in insulin secretion. (2014)
  • Author(s): Fushun Fan, Kohichi Matsunaga, Tetsuro Izumi
  • Organizer: 群馬大学大学院理工学府・生体調節研究所第19回生命科学セミナー
  • Place of Presentation: 群馬大学（群馬県前橋市）
  • Year and Date: 2014-07-25
• [Presentation] 膵B細胞におけるRab27a-GAP新規結合タンパク質の機能解析。 (2014)
  • Author(s): 山岡 真美、岡本 光弘、安藤 朋海、寺林 健、松永 耕一、泉 哲郎、仁木 一郎、石崎 敏理、木村 俊秀
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: リーガロイヤルホテル（大阪府大阪市）
  • Year and Date: 2014-05-24
• [Presentation] The relationship between docking and fusion of insulin granules in living beta cells. (2013)
  • Author(s): Tetsuro Izumi and Kouichi Mizuno
  • Organizer: Beta Cell Workshop
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] The Rab27a effector exophilin7 promotes fusion of insulin granules with out stable docking to the plasma membrane. (2012)
  • Author(s): Hao Wang, Tetsuro Izumi, et al.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress / 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes.
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-11-27
• [Presentation] 膵β細胞に発現するRab27aエフェクターExophilin7遺伝子欠損マウスの解析 (2012)
  • Author(s): 石崎玲、王 昊、泉哲郎
  • Organizer: 平成24年度日本生化学会関東支部例会
  • Place of Presentation: 群馬大学(群馬県)
  • Year and Date: 2012-06-23
• [Presentation] 膵β細胞に発現するRab27aエフェクターExophilin7遺伝子欠損マウスの解析 (2012)
  • Author(s): 王昊、泉哲郎, 他
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2012-05-19
• [Presentation] Roles of multiple Rab27a effectors 1n insulin granule exocytosis. (2012)
  • Author(s): 泉 哲郎
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)(招待講演)
  • Year and Date: 2012-05-17
• [Presentation] Exophilin7 promotes fusion of undocked granule in pancreatic SS cells. (2012)
  • Author(s): Ray Ishizaki, Tetsuro Izumi, et al.
  • Organizer: Joint Meeting of The 45^<th> Annual Meeting of the Japanese Society of Developmental Biologists & The 64^<th> Annual Meeting of the Japan Society for Cell Biology
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
• [Presentation] インスリン分泌顆粒の開口放出機構
  • Author(s): 泉 哲郎
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本（熊本県）
  • Invited
• [Presentation] グラニュフィリン陽性顆粒の動態解析
  • Author(s): 水野 広一、泉 哲郎
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: ウインクあいち（愛知県）
• [Presentation] ケミカルライブラリーを用いた網羅的な新規インスリン分泌制御化合物の探索
  • Author(s): 松永 耕一、斎藤 臣雄、長田 裕之、泉 哲郎
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 分泌顆粒の開口放出前過程
  • Author(s): 泉 哲郎
  • Organizer: 細胞内ロジスティクス・シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県）
  • Invited
• [Remarks] 群馬大学生体調節研究所遺伝生化学分野ホームページ
  • URL: http://molend.showa.gunma-u.ac.jp/
• [Remarks] 群馬大学生体調節研究所 遺伝生化学分野 泉研究室
  • URL: http://molend.showa.gunma-u.ac.jp/