Mechanisms of secretory granule maturation by lipid analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K11973
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Nihon University
• Principal Investigator: KATSUMATA-KATO Osamu (勝俣治) 日本大学, 松戸歯学部, 准教授 (70349968)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 唾液腺 / 耳下腺 / 分泌顆粒 / 成熟過程 / カテプシンB

Outline of Final Research Achievements

Acinar cells of the parotid gland have amylase in their secretory granules (SGs). SGs generate at the Golgi apparatus and then they mature. Maturation processes of SG have fusion of granules and membrane remodeling. SGs in the parotid glands cause membrane remodeling within 3 hours after generation, and VAMP2, which is involved in exocytosis, is enriched in the granule membrane. It is considered that the membrane remodeling prepares for the exocytosis of SGs, but detail of the process is unknown. Cathepsin B is degradative enzyme that locates in lysosome. Mannose-6-phosphate (M6P) is added to pro-cathepsin B at Golgi apparatus to transport into lysosome. Pro-cathepsin B is transported to lysosomes via SGs in the parotid glands. Then, we postulated that non-M6P tagged pro-cathepsin B remains in SGs. In this study, it is confirmed that the secreted pro-cathepsin B has no M6P tagged. Our finding indicates that newly-formed SGs have capacity of secretion before membrane remodeling.

Free Research Field

口腔生理学

Academic Significance and Societal Importance of the Research Achievements

膵臓β細胞の破壊を原因とする１型糖尿病の治療には遺伝子治療が望まれる。代償臓器の候補に挙げられる唾液腺の適応までには顆粒濃縮機構の解明，刺激依存的な内分泌経路の解明，そして唾液腺特異的な遺伝子発現法の開発という３つの大きな課題が残されている。本研究では『唾液腺の分泌顆粒にインスリンを濃縮させる。』という課題の１つである成熟機構の解明を目指した。顆粒成熟モデルの解明は神経や内分泌細胞といった他の分泌研究分野へ与える影響も強く，近い将来必ず行われるだろう遺伝子治療に向けた重要な基礎研究の１つに位置づけられると考えている。