Regulated secretion is a complex and fundamental biological process that allows the release of functionally important intracellular products (e.g., neurotransmitters, hormones and digestive enzymes) into the extracellular space. An extensive number of clinical disorders result from the disruption of this process. Among the large number of different regulated secretory organelles, only a few of them have been specifically characterized. The abundant, large and protein-rich ZGs of the exocrine pancreas are well suited for proteomic studies, but have only recently been analyzed in greater detail by a combination of organelle purification, protein separation, mass spectrometry, quantitation and validation experiments. These studies have identified and confirmed several new 'players', especially at the granule membrane, with a potential function in granule biogenesis and regulated secretion. Some of the discovered proteins have a known function in other subcellular locations, indicating multitasking of proteins. Importantly, besides a role in granule formation, additional functions in host defence and regulation are emerging, once the proteins have been released into the intestinal tract. In addition, proteins thought to be specific for ZGs and acinar cells have been identified in other cells and compartments. With the identification of the vast majority (but not all) of the 'players' involved in ZG biogenesis and secretion, the stage is now set for a thorough biological/functional analysis of their interplay. There is a critical need for validation experiments and functional studies to provide a better understanding of the processes of ZG formation, sorting/packaging of cargo, exocytosis and membrane fusion, and to generate a more complete picture of the ZG architecture. These studies will represent the basis for the identification of new and specific biomarkers for diagnosis, early detection and discovery of potential therapeutic targets for pancreatic diseases.
Expert Rev Proteomics. 2010;7(5):735-747. © 2010
Expert Reviews Ltd.
Cite this: Proteomic Analysis of Zymogen Granules - Medscape - Oct 01, 2010.