Proteomic Analysis of Zymogen Granules

María Gómez-Lázaro; Cornelia Rinn; Miguel Aroso; Francisco Amado; Michael Schrader


Expert Rev Proteomics. 2010;7(5):735-747. 

In This Article

Zymogen Granules in a Nutshell

The acinar cells of the exocrine pancreas are among the cells with the highest rate of protein synthesis in higher organisms and target more than 90% of newly synthesized proteins to the secretory pathway.[1] They are 'specialists' in the synthesis, mass packaging/sorting, storage and regulated secretion of a complex mixture of different digestive enzymes and isoenzymes. This variety of digestive enzymes is packaged in a condensed and predominantly inactive form into large (~1 µm in diameter) secretory organelles, so-called zymogen granules (ZGs) (Figure 1A) (for a comprehensive review,see [2–4]). ZGs contain five functional groups of hydrolytic enzymes and pro-enzymes (endo- and exo-proteases, lipases, glycosidases and RNases), including amylase, the most prominent ZG content protein, as well as trypsinogen, chymotrypsinogen, carboxypeptidases, esterases, lipases, RNase and DNase ( Table 1 ). The synthesis and release of digestive enzymes is regulated by gastrointestinal hormones and neurotransmitters (e.g., cholecystokinin and acetylcholine).[5] Secretagogue stimulation of the acinar cells causes an elevation of intracellular Ca2+ concentration, which in turn triggers fusion of the granules with the apical plasma membrane, leading to exocytosis.[6] The digestive enzymes are then released via the pancreatic duct system into the small intestine, where conversion of trypsinogen to trypsin is mediated by proteolytic cleavage via enterokinase (enteropeptidase),[7] an enzyme of the duodenal mucosa. Activated trypsin then proteolytically cleaves and activates the other zymogen enzymes.

Figure 1.

Ultrastructure of ZGs and ZG subfractions. (A) Electron micrograph of ZGs in the apical region of rat pancreatic acinar cells surrounding an acinar lumen (L). (B) Electron micrograph of a crude ZG fraction isolated from rat pancreas. Fine structure of ZG membranes (C) from the pellet and ZG content proteins (D) from the supernatant of a ZG subfractionation. (E) Adjustment to a slightly acidic pH of 5.9 initiates aggregation of the ZG content proteins. Note the formation of round aggregates of a nearly uniform size (0.6–0.8 µm).
L: Acinar lumen; ZG: Zymogen granule.
(C–E) reproduced from [11] with permission from Elsevier.