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Elucidation of formation and degradation mechanism of peptide hormone-containing secretory granules (the life of secretory granules)

Research Project

Project/Area Number 16K08078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionNihon University

Principal Investigator

GOMI Hiroshi  日本大学, 生物資源科学部, 教授 (90293240)

Co-Investigator(Kenkyū-buntansha) 安井 禎  日本大学, 生物資源科学部, 准教授 (70434107)
Research Collaborator TORII Seiji  
HOSAKA Masahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords内分泌細胞 / 分泌顆粒 / フォグリン / セクレトグラニン / ペプチドホルモン / トランスゴルジネットワーク / リソソーム / 遺伝子欠損マウス / 活性アミン産生細胞 / SNAREタンパク質 / IA2ファミリータンパク質 / グラニンタンパク質 / 細胞・組織 / 応用動物 / 生理活性 / 遺伝子 / 解剖学
Outline of Final Research Achievements

We have analyzed the properties of secretory granules devoid of phogrin and secretogranin 3 expressed in pancreatic beta cells. We have found novel findings of intracellular lysosomal morphology in phogrin-deficient beta cells. Our findings were different from those reported in previous studies showing drastic changes in lysosomal morphology. On the other hand, secretogranin 3-deficient beta cells were suggested a change in neutral sugar localization in the granule membranes. It has been clarified that secretogranin 3 is expressed in active amine producing cells in nerves, adrenal glands, in addition to peptide hormone-producing cells. Secretogranin 3 was revealed to be predominantly expressed in noradrenaline cells in adrenal gland. Furthermore, we focused on the expression of secretogranin 3 in the central nervous system and found expression in cerebellar glial cells including Bergmann glia.

Academic Significance and Societal Importance of the Research Achievements

内分泌細胞における分泌顆粒の細胞内輸送や開口放出に関わる分子基盤や分泌調節機序に関しては、学術的知見の蓄積が豊富である。これに対し、分泌顆粒の形成から分解の機構の詳細は十分に分かっていなかった。本研究では、マウスリバースジェネティクスを駆使し、分泌顆粒膜に局在し、ペプチドホルモンのソーティングや凝集に関わっている分子がこの機構にどのように関わっているのかについて、一定の考察をすることができた。得られた結果は、生理的なホルモン産生低下の機序や内分泌代謝疾患の病態の理解にも繋がる基礎的な知見といえる。また、電顕糖質細胞化学により、内分泌顆粒の性状を解析した前例は無く、斬新性を有する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Culture in 10% O2 enhances the production of active hormones in neuro-endocrine cells by up-regulating the expression of processing enzymes2019

    • Author(s)
      Sato E, Maeda Y, Sato Y, Hinata A, Gomi H, Koga D, Torii S, Watanabe T, Hosaka M
    • Journal Title

      Biochem. J.

      Volume: 476 Issue: 5 Pages: 827-842

    • DOI

      10.1042/bcj20180832

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The pseudophosphatase phogrin enables glucose-stimulated insulin signaling in pancreatic β cells2018

    • Author(s)
      Torii Seiji、Kubota Chisato、Saito Naoya、Kawano Ayumi、Hou Ni、Kobayashi Masaki、Torii Ryoko、Hosaka Masahiro、Kitamura Tadahiro、Takeuchi Toshiyuki、Gomi Hiroshi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 16 Pages: 5920-5933

    • DOI

      10.1074/jbc.ra117.000301

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired processing of prohormones in secretogranin III null mice causes maladaptation to an inadequate diet and stress.2018

    • Author(s)
      Yoshinori Maeda, Saki Kudo, Ken Tsushima, Eri Sato, Chisato Kubota, Aika Kayamori, Hiroki Bochimoto, Daisuke Koga, Seiji Torii, Hiroshi Gomi, Tsuyoshi Watanabe, Masahiro Hosaka
    • Journal Title

      Endocrinology

      Volume: 159 Issue: 2 Pages: 1213-1227

    • DOI

      10.1210/en.2017-00636

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Canine salivary glands: analysis of Rab and SNARE protein expression and SNARE complex formation with diverse tissue properties.2017

    • Author(s)
      Hiroshi Gomi, Hiromi Osawa, Rie Uno, Tadashi Yasui, Masahiro Hosaka, Seiji Torii, Azuma Tsukise
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 65 Issue: 11 Pages: 637-653

    • DOI

      10.1369/0022155417732527

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultrastructure and immunohistochemical characterization of proteins concerned with the secretory machinery in goat ceruminous glands.2017

    • Author(s)
      Tadashi Yasui, Hiroshi Gomi, Taishi Kitahara, Azuma Tsukise
    • Journal Title

      European Journal of Histochemistry

      Volume: 61 Issue: 3 Pages: 222-230

    • DOI

      10.4081/ejh.2017.2828

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 分泌顆粒蛋白質フォグリンによるインスリン分泌とシグナルの連結機構2018

    • Author(s)
      久保田知里、齊藤直也、河野あゆみ、竹内利行、小林雅樹、北村忠弘、穂坂正博、五味浩司、鳥居征司
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] イヌ涙腺における糖質ならびに免疫組織化学的解析2018

    • Author(s)
      安井禎、五味浩司
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] イヌ口腔腺におけるRabおよびSNAREタンパク質の発現解析2018

    • Author(s)
      五味浩司、大澤裕美、宇野理恵、安井禎、鳥居征司、穂坂正博、月瀬東
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ニワトリ内分泌器官におけるセクレトグラニンIIIの発現 解析2016

    • Author(s)
      五味 浩司、安井 禎、鳥居 征司、穂坂 正博
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生物資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] シバヤギ耳道腺における抗菌物質と分泌制御タンパク質の 免疫組織化学的解析2016

    • Author(s)
      安井 禎、五味 浩司
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生物資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Remarks] 日本大学大学院獣医学研究科獣医学専攻

    • URL

      http://www.brs.nihon-u.ac.jp/education/graduate_schools/veterinary_medicine/vm.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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