Format

Send to

Choose Destination
Sci Rep. 2018 Aug 9;8(1):11903. doi: 10.1038/s41598-018-30370-4.

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

Author information

1
Department of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
2
Goodman Cancer Research Center and Department of Biology, McGill University, Montreal, QC, H3A 1A3, Canada.
3
Department of Medicine, Mayo Clinic, Scottsdale, Arizona, USA. singh.vijay@mayo.edu.

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.

PMID:
30093675
PMCID:
PMC6085363
DOI:
10.1038/s41598-018-30370-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center