c-Src regulates cargo transit via the Golgi in pancreatic acinar cells

Abstract The exocrine pancreatic acinar cell is unique for its rapid protein synthesis and packaging in zymogen granules (ZGs). However, while crucial to the pathogenesis of pancreatitis, the signaling involved in the transit of proteins via the Golgi is poorly understood in these cells. Noting the...

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Autores principales:	Sergiy Kostenko, Chan C. Heu, Jordan R. Yaron, Garima Singh, Cristiane de Oliveira, William J. Muller, Vijay P. Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc04a334a95742faa24197deda9920c2
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spelling	oai:doaj.org-article:cc04a334a95742faa24197deda9920c22021-12-02T15:08:12Zc-Src regulates cargo transit via the Golgi in pancreatic acinar cells10.1038/s41598-018-30370-42045-2322https://doaj.org/article/cc04a334a95742faa24197deda9920c22018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30370-4https://doaj.org/toc/2045-2322Abstract The exocrine pancreatic acinar cell is unique for its rapid protein synthesis and packaging in zymogen granules (ZGs). However, while crucial to the pathogenesis of pancreatitis, the signaling involved in the transit of proteins via the Golgi is poorly understood in these cells. Noting the evidence of c-Src in regulating transit of cargo via the Golgi in other systems, we explored this in acinar cells. Stimulation of ZG formation with dexamethasone activated Src and increased the Golgi area in acinar cells. c-Src localized to the microsomes of acinar cells on immunofluorescence and subcellular fractionation. While other Src family members had no effect on the Golgi markers P115 and GM130, active c-Src increased the Golgi area these stained, extending them into the ER. Src inhibition reduced amylase staining outside the Golgi and increased it in a stack like Golgi morphology. In vivo pharmacologic inhibition or acinar specific genetic deletion of c-Src reduced ZG number and staining of amylase in ZGs along with increasing amylase retention in the microsomal fraction. Morphologically this was associated with smaller Golgi stacks, and dilation of the endoplasmic reticulum. Therefore the role c-Src regulated Golgi function, ZG formation and microsomal zymogen transit in acinar cells needs to be explored in pancreatitis.Sergiy KostenkoChan C. HeuJordan R. YaronGarima SinghCristiane de OliveiraWilliam J. MullerVijay P. SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sergiy Kostenko Chan C. Heu Jordan R. Yaron Garima Singh Cristiane de Oliveira William J. Muller Vijay P. Singh c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
description	Abstract The exocrine pancreatic acinar cell is unique for its rapid protein synthesis and packaging in zymogen granules (ZGs). However, while crucial to the pathogenesis of pancreatitis, the signaling involved in the transit of proteins via the Golgi is poorly understood in these cells. Noting the evidence of c-Src in regulating transit of cargo via the Golgi in other systems, we explored this in acinar cells. Stimulation of ZG formation with dexamethasone activated Src and increased the Golgi area in acinar cells. c-Src localized to the microsomes of acinar cells on immunofluorescence and subcellular fractionation. While other Src family members had no effect on the Golgi markers P115 and GM130, active c-Src increased the Golgi area these stained, extending them into the ER. Src inhibition reduced amylase staining outside the Golgi and increased it in a stack like Golgi morphology. In vivo pharmacologic inhibition or acinar specific genetic deletion of c-Src reduced ZG number and staining of amylase in ZGs along with increasing amylase retention in the microsomal fraction. Morphologically this was associated with smaller Golgi stacks, and dilation of the endoplasmic reticulum. Therefore the role c-Src regulated Golgi function, ZG formation and microsomal zymogen transit in acinar cells needs to be explored in pancreatitis.
format	article
author	Sergiy Kostenko Chan C. Heu Jordan R. Yaron Garima Singh Cristiane de Oliveira William J. Muller Vijay P. Singh
author_facet	Sergiy Kostenko Chan C. Heu Jordan R. Yaron Garima Singh Cristiane de Oliveira William J. Muller Vijay P. Singh
author_sort	Sergiy Kostenko
title	c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
title_short	c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
title_full	c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
title_fullStr	c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
title_full_unstemmed	c-Src regulates cargo transit via the Golgi in pancreatic acinar cells
title_sort	c-src regulates cargo transit via the golgi in pancreatic acinar cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/cc04a334a95742faa24197deda9920c2
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c-Src regulates cargo transit via the Golgi in pancreatic acinar cells

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