Elucidation of formation and degradation mechanism of peptide hormone-containing secretory granules (the life of secretory granules)
| Project/Area Number |
16K08078
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Integrative animal science
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| Research Institution | Nihon University |
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Principal Investigator |
GOMI Hiroshi 日本大学, 生物資源科学部, 教授 (90293240)
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| Co-Investigator(Kenkyū-buntansha) |
安井 禎 日本大学, 生物資源科学部, 准教授 (70434107)
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| Research Collaborator |
TORII Seiji
HOSAKA Masahiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(11 results)
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[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
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Journal Title
Endocrinology
Volume: 159
Issue: 2
Pages: 1213-1227
DOI
Related Report
Peer Reviewed / Open Access
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