A special seminar was given on behalf of the Cardiff Hub by Professor Alexei Tepikin, University of Liverpool, on 14th November.
Ca2+ signalling cascade is important for the physiology and pathophysiology of exocrine pancreas. Store operated Ca2+ entry (SOCE) is the main Ca2+ entry pathway in pancreatic acinar cells and in pancreatic ductal adenocarcinoma (PDAC) cells. SOCE activation requires direct interaction of STIM and Orai proteins that occur in junctions between the endoplasmic reticulum and the plasma membrane (ER-PM junctions). The main conclusions of the lecture are:
Ca2+ signalling mediates efficient stimulus – metabolism coupling in pancreatic acinar cells.
STIM1 and Orai1 display polarized distribution in pancreatic acinar cells. STIM1-containing ER-PM junctions are located in the basolateral regions of pancreatic acinar cells.
SOCE is important for cell damage of the acinar cells by the inducers of acute pancreatitis.
In migrating pancreatic ductal adenocarcinoma cells (PANC1 cells) STIM1 puncta (i.e. STIM-competent ER-PM junctions) are frequently found at the leading edge of the cells. Saltatory formation of STIM1 puncta was observed in this region.
ER-PM junctions were found in close proximity to the edge of polymerized actin and in close proximity to focal adhesions.
Inhibition of IP3Rs and inhibition of SOCE suppress migration of pancreatic ductal adenocarcinoma cells.
A selected set of slides are below.