Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells
Abstract Rab7 is known to function in the autophagy and endocytosis pathways in eukaryocytes and is related to various diseases. We recently reported that Rab7 plays a protective role against acute pancreatitis. However, its physiological function in exocytic cells remains unclear. Therefore, we inv...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49520-4 |
| _version_ | 1797388375720722432 |
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| author | Kenichi Takahashi Hirosato Mashima Masanari Sekine Takeshi Uehara Takeharu Asano Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi |
| author_facet | Kenichi Takahashi Hirosato Mashima Masanari Sekine Takeshi Uehara Takeharu Asano Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi |
| author_sort | Kenichi Takahashi |
| collection | DOAJ |
| description | Abstract Rab7 is known to function in the autophagy and endocytosis pathways in eukaryocytes and is related to various diseases. We recently reported that Rab7 plays a protective role against acute pancreatitis. However, its physiological function in exocytic cells remains unclear. Therefore, we investigated the role of Rab7 in pancreas-specific Rab7 knockout mice (Rab7Δpan). Immunofluorescence microscopy revealed that Rab7 colocalized with amylase in pancreatic acinar cells of wild-type mice, but not in Rab7Δpan mice. Western blotting confirmed Rab7 localization in the zymogen granule (ZG) membranes of wild-type mice. Cholecystokinin (CCK)-stimulated amylase secretion examined using isolated pancreatic acini was similar in Rab7Δpan and wild-type mice. In contrast, electron microscopy revealed that the diameters of ZGs were shorter and the number of ZGs was larger in the pancreatic acinar cells of Rab7Δpan mice than in those of wild-type mice. However, the number of ZGs decreased in both Rab7Δpan and wild-type mice after 24 h of starvation. In addition, the amount of amylase in the pancreas was decreased in both Rab7Δpan and wild-type mice. These data indicate that Rab7 localized on ZGs plays a crucial role in the maturation of ZGs but not in their autophagy or regulated exocytosis in pancreatic acinar cells. |
| first_indexed | 2024-03-08T22:39:55Z |
| format | Article |
| id | doaj.art-ea377388f56c424c87751497e8ddbd0c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T22:39:55Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ea377388f56c424c87751497e8ddbd0c2023-12-17T12:15:21ZengNature PortfolioScientific Reports2045-23222023-12-0113111010.1038/s41598-023-49520-4Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cellsKenichi Takahashi0Hirosato Mashima1Masanari Sekine2Takeshi Uehara3Takeharu Asano4Ge-Hong Sun-Wada5Yoh Wada6Hirohide Ohnishi7Department of Gastroenterology, Akita University Graduate School of MedicineDepartment of Gastroenterology, Jichi Medical University Saitama Medical CenterDepartment of Gastroenterology, Jichi Medical University Saitama Medical CenterDepartment of Gastroenterology, Jichi Medical University Saitama Medical CenterDepartment of Gastroenterology, Jichi Medical University Saitama Medical CenterDepartment of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women’s CollegeDivision of Biological Science, Institute of Scientific and Industrial Research, Osaka UniversityDepartment of Gastroenterology, Jichi Medical University Saitama Medical CenterAbstract Rab7 is known to function in the autophagy and endocytosis pathways in eukaryocytes and is related to various diseases. We recently reported that Rab7 plays a protective role against acute pancreatitis. However, its physiological function in exocytic cells remains unclear. Therefore, we investigated the role of Rab7 in pancreas-specific Rab7 knockout mice (Rab7Δpan). Immunofluorescence microscopy revealed that Rab7 colocalized with amylase in pancreatic acinar cells of wild-type mice, but not in Rab7Δpan mice. Western blotting confirmed Rab7 localization in the zymogen granule (ZG) membranes of wild-type mice. Cholecystokinin (CCK)-stimulated amylase secretion examined using isolated pancreatic acini was similar in Rab7Δpan and wild-type mice. In contrast, electron microscopy revealed that the diameters of ZGs were shorter and the number of ZGs was larger in the pancreatic acinar cells of Rab7Δpan mice than in those of wild-type mice. However, the number of ZGs decreased in both Rab7Δpan and wild-type mice after 24 h of starvation. In addition, the amount of amylase in the pancreas was decreased in both Rab7Δpan and wild-type mice. These data indicate that Rab7 localized on ZGs plays a crucial role in the maturation of ZGs but not in their autophagy or regulated exocytosis in pancreatic acinar cells.https://doi.org/10.1038/s41598-023-49520-4 |
| spellingShingle | Kenichi Takahashi Hirosato Mashima Masanari Sekine Takeshi Uehara Takeharu Asano Ge-Hong Sun-Wada Yoh Wada Hirohide Ohnishi Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells Scientific Reports |
| title | Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| title_full | Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| title_fullStr | Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| title_full_unstemmed | Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| title_short | Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| title_sort | rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells |
| url | https://doi.org/10.1038/s41598-023-49520-4 |
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