A study of a calcium-binding protein-regulated network in collagen secretion
| Project/Area Number |
18H02135
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 38030:Applied biochemistry-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Shibata Hideki 名古屋大学, 生命農学研究科, 准教授 (30314470)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | カルシウム / コラーゲン / COPII / 分泌経路 / 小胞体 / COPII小胞 |
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| Outline of Final Research Achievements |
Collagens are structural proteins that constitute approximately 25% of human dry body weight and are secreted from the endoplasmic reticulum to the extracellular space via the Golgi apparatus. In this study, we aimed to elucidate the molecular mechanisms by which calcium-responsive regulators, mainly the calcium-binding protein ALG-2, control export of collagens from the endoplasmic reticulum, by searching for target molecules of ALG-2 by its binding motifs and by using proximity-dependent labeling methods coupled with mass spectrometry. The protein-protein interaction networks and subcellular localization of multiple candidate regulators and their functions were elucidated by biochemical and molecular cell biological approaches.
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| Academic Significance and Societal Importance of the Research Achievements |
分泌蛋白質のほとんどは、小胞体で合成されゴルジ体を経由して細胞外に分泌される。細胞外マトリクスの主要成分である線維性コラーゲンは、その長さが300 nmにもおよび、小胞体からどのように搬出され細胞外まで輸送されるのか不明であった。近年、線維性コラーゲン輸送の制御因子の同定がすすめられ、その中でALG-2はカルシウムに応答する因子である。本研究では、ALG-2の新たな標的蛋白質を同定し、小胞体内腔のカルシウム濃度の恒常性維持に関わる可能性を示した。また、小胞体からの搬出の制御蛋白質候補も新たに同定されており、線維症などコラーゲン分泌の異常が関連する疾患の新奇の創薬標的になることも期待される。
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Report
(4 results)
Research Products
(13 results)
