1. RASEF/Rab45 regulates the formation and sorting of zymogen granules and secretion of digestive enzymes by pancreatic acinar cells.
- Author
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Sato K, Kadowaki T, Takenaka M, Konishi M, Ando M, Onodera T, and Tsukuba T
- Subjects
- Animals, Mice, rab GTP-Binding Proteins metabolism, rab GTP-Binding Proteins genetics, Endoplasmic Reticulum metabolism, Pancreatitis metabolism, Pancreatitis pathology, Pancreatitis chemically induced, Pancreas metabolism, Pancreas, Exocrine metabolism, Exocytosis, Protein Transport, Trypsinogen metabolism, Male, Lysosomes metabolism, Acinar Cells metabolism, Mice, Knockout, Secretory Vesicles metabolism
- Abstract
The pancreas is a glandular organ with both endocrine and exocrine functions. Researchers have investigated the roles of several Rab proteins, which are major regulators of membrane trafficking, in pancreatic exocytosis of zymogen granules in exocrine cells, also known as acinar cells. However, detailed molecular mechanisms mediated by Rab proteins are not fully understood. RASEF/Rab45 is an atypical Rab GTPase that contains N-terminal EF-hand and coiled-coil domains, as well as a C-terminal Rab-GTPase domain. In this study, we investigated the in vivo role of RASEF in pancreatic acinar cells using RASEF-knockout (KO) mice. Morphological analyses revealed that pancreatic acinar cells in RASEF-KO mice had an increased number of zymogen granules and abnormal formations of organelles, such as the endoplasmic reticulum (ER) and lysosomes. Biochemical analyses showed that ER proteins were decreased, but digestive enzymes were increased in the RASEF-KO pancreas. Moreover, trypsinogen was activated and co-localized with the endo-lysosomal marker LAMP1 in RASEF-KO pancreas. Upon cerulein administration to induce acute pancreatitis, impaired enzyme release from the pancreas was observed in the serum of RASEF-KO mice. These findings suggest that RASEF likely regulates the formation and sorting of zymogen granules and secretion of digestive enzymes by pancreatic acinar cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomoko Kadowaki reports financial support was provided by Japan Society for the Promotion of Science. Keiko Sato reports financial support was provided by Japan Society for the Promotion of Science. Takayuki Tsukuba reports financial support was provided by Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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