Discovery of the Cell Secretion Machinery

Abstract

Cellular secretion is fundamental to the very existence of an organism, regulating important physiological functions such as reproduction, digestion, energy production, growth, neurotransmission, hormone release, water and ion transport, etc., all required for the survival and maintenance of homeostasis within an organism. Understanding how cells secrete has therefore been of paramount importance, and only in the past decade, the molecular mechanism of the process has come to light with the discovery of the ‘porosome,’ the universal secretion machinery. Porosomes are supramolecular nanometer-size structures at the cell plasma membrane, where secretory vesicles fuse to release their contents such as neurotransmitters, hormones, or enzymes from the cell. Porosomes were first discovered at the plasma membrane of the digestive enzyme-secreting, live acinar cells of the exocrine pancreas, using atomic force microscopy. Immuno-atomic force microscopy, has conclusively demonstrated the release of digestive enzymes through the porosome opening in pancreatic acinar cells. Subsequent studies using electron microscopy, has further confirmed the presence of porosomes, and determined their function as the cells secretory apparatus. Studies have since determined the structure and dynamics of porosomes at nanometer resolution in live cells, their chemical composition, and their structural and functional reconstitution in artificial lipid membrane preparations. Porosomes have been determined to be the universal secretory machinery in cells, and besides pancreatic acinar cells, have been demonstrated in every secretory cell examined such as neurons, growth hormone cells of the pituitary gland, chromaffin cells, mast cells, and the insulin-secreting -cells of endocrine pancreas. The discovery of the porosome finally provides a molecular understanding of the secretory process in cells.