Pancreatic Acinar Cell Protein Synthesis, Intracellular Transport, and Export

A key function of the exocrine pancreas is the production of digestive enzymes. The pancreatic acinar cell synthesizes, stores, and secretes the proenzymes and enzymes needed to digest dietary proteins, carbohydrates, and lipids. Meeting these functional requirements necessitates that the acinar cell has very high rates of protein synthesis and export. Nascent proteins undergo folding, select modifications, concentration, segregation from other classes of proteins, and vectorial movement before reaching their final destination in secretory (zymogen) granules. These are concentrated in the apical pole of the acinar cell. Eating stimulates neural and hormonal pathways that mediate acinar cell zymogen granule exocytosis into the pancreatic duct. The exocrine pancreas has two major physiologic functions: it supplies the proenzymes and enzymes needed for digesting dietary lipids, carbohydrates, and proteins; and secretes a bicarbonate-rich fluid that neutralizes acidic gastric secretions and thus provides the correct pH for intestinal digestion by pancreatic enzymes. The acinar cell has been a model system for foundational studies of protein synthesis and export. After electron microscopy was developed, for example, cell biologists first visualized organelles and established their function by studying acinar cells (Figure 1). Here, we focus on acinar cell protein synthesis, trafficking, and processing in the pancreatic acinar cell necessary for its central role in producing digestive enzymes. We present results primarily obtained using rodent acinar cells, though the limited data from human acinar cells suggest the functions are likely the