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

Sergiy Kostenko, Chan C. Heu, Jordan R. Yaron, Garima Singh, Cristiane de Oliveira, William J. Muller, Vijay Prem Singh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number11903
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Acinar Cells
Secretory Vesicles
Amylases
Pancreatitis
Staining and Labeling
Enzyme Precursors
Product Packaging
Microsomes
Endoplasmic Reticulum
Dexamethasone
Fluorescent Antibody Technique
Dilatation
Proteins
Inhibition (Psychology)

ASJC Scopus subject areas

  • General

Cite this

Kostenko, S., Heu, C. C., Yaron, J. R., Singh, G., de Oliveira, C., Muller, W. J., & Singh, V. P. (2018). c-Src regulates cargo transit via the Golgi in pancreatic acinar cells. Scientific Reports, 8(1), [11903]. https://doi.org/10.1038/s41598-018-30370-4

c-Src regulates cargo transit via the Golgi in pancreatic acinar cells. / Kostenko, Sergiy; Heu, Chan C.; Yaron, Jordan R.; Singh, Garima; de Oliveira, Cristiane; Muller, William J.; Singh, Vijay Prem.

In: Scientific Reports, Vol. 8, No. 1, 11903, 01.12.2018.

Research output: Contribution to journalArticle

Kostenko, S, Heu, CC, Yaron, JR, Singh, G, de Oliveira, C, Muller, WJ & Singh, VP 2018, 'c-Src regulates cargo transit via the Golgi in pancreatic acinar cells', Scientific Reports, vol. 8, no. 1, 11903. https://doi.org/10.1038/s41598-018-30370-4
Kostenko S, Heu CC, Yaron JR, Singh G, de Oliveira C, Muller WJ et al. c-Src regulates cargo transit via the Golgi in pancreatic acinar cells. Scientific Reports. 2018 Dec 1;8(1). 11903. https://doi.org/10.1038/s41598-018-30370-4
Kostenko, Sergiy ; Heu, Chan C. ; Yaron, Jordan R. ; Singh, Garima ; de Oliveira, Cristiane ; Muller, William J. ; Singh, Vijay Prem. / c-Src regulates cargo transit via the Golgi in pancreatic acinar cells. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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