RASEF/Rab45 regulates the formation and sorting of zymogen granules and secretion of digestive enzymes by pancreatic acinar cells.
Biochim Biophys Acta Mol Basis Dis
; 1870(7): 167310, 2024 10.
Article
en En
| MEDLINE
| ID: mdl-38901651
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Intercambio de Guanina Nucleótido ras
/
Vesículas Secretoras
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Células Acinares
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
/
Biochim. biophys. acta, Mol. basis dis
/
Biochimica et biophysica acta. Molecular basis of disease
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón