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

Proteomics of ZG Proteins in Pancreatic Juice

The PJ constitutes a rich source of secreted ZG proteins coming from the pancreatic acinar cells, solubilized in an aqueous bicarbonate solution delivered by the cells of the pancreatic duct system. The alkaline juice neutralizes the gastric acid and allows effective enzyme activation initiated by the processing of trypsinogen in the intestine.[5,7] Extensive studies on the PJ, mostly by early 2D-PAGE in the late 1970–1980s, led to the discovery of several pancreatic enzymes.[50,51,87] Recently, the interest in PJ rose again, as the metabolic products of pancreatic diseases, for example, pancreatitis- or pancreatic cancer-specific proteins (via shed cancer cells), are released into PJ. Thus, PJ represents a rich and relatively easily accessible source for the identification of new and specific biomarkers for diagnosis, early detection and the discovery of potential therapeutic targets for pancreatic diseases.[88–91] Using 1-DE and LC-MS/MS, Gronborg and colleagues provided a comprehensive study of the protein constituents in human PJ.[90] In addition, quantitative approaches were applied to human PJ from controls and patients with pancreatitis or cancer. In these studies, difference in-gel electrophoresis (DIGE)[92] or ICAT was used.[88,89] Furthermore, SELDI-TOF-MS has been applied to identify novel protein peaks in PJ to distinguish between samples from cancer patients and controls.[93] Many pancreatic (ZG) enzymes are prominent constituents of PJ. Recently, chymotrypsin C (caldecrin) obtained much attention as a putative regulator of cationic trypsin in the digestive tract. Mutated versions have been associated with the development of chronic pancreatitis.[94–96] Other ZG proteins found in PJ are ZGM constituents. GP2, the major ZGM protein, is a GPI-anchored protein with both membrane and soluble forms[46] similar to integral membrane-associated protein 1 (ITMAP1), a ZG transmembrane protein.[97] As an essential function for GP2 in ZG biogenesis and secretion could not be confirmed,[98] a new role in host defence by binding to bacterial fimbriae has been proposed.[25] Very recently, GP2 was identified as a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria.[99] Furthermore, GP2, a homologue of uromodulin/Tamm–Horsfall protein from the kidney, has recently been identified as an autoantigen in Crohn's disease.[100] Syncollin, another membrane-bound ZG protein identified in PJ,[90] represents a unique protein with a role in compound exocytosis.[101,102] Interestingly, it has been reported to interact with GP2[32] and was also found in neutrophilic granulocytes.[103] The proteomic analysis of ZG proteins also revealed a few enzymes that had been identified in PJ but were never shown previously to be in ZGs (e.g., chymopasin and γ-glutamyl hydrolase).[35]