Mucous granule exocytosis and CFTR expression in gallbladder epithelium

A mechanistic model of mucous granule exocytosis by columnar epithelial cel ls must take into account the unique physical-chemical properties of mucin glycoproteins and the resultant mucus gel. In particular, any model must ex plain the intracellular packaging and the kinetics of release of these larg e, heavily charged species. We studied mucous granule exocytosis in gallbla dder epithelium, a model system for mucus secretion by columnar epithelial cells. Mucous granules released mucus by merocrine exocytosis in mouse gall bladder epithelium when examined by transmission electron microscopy. Spher ules of secreted mucus larger than intracellular granules were noted on sca nning electron microscopy. Electron probe microanalysis demonstrated increa sed calcium concentrations within mucous granules. Immunofluorescence micro scopic studies revealed intracellular colocalization of mucins and the cyst ic fibrosis transmembrane conductance regulator (CFTR), Confocal laser immu nofluorescence microscopy confirmed colocalization, These observations sugg est that calcium in mucous secretory granules provides cationic shielding t o keep mucus tightly packed. The data also suggests CFTR chloride channels are present in granule membranes. These observations support a model in whi ch influx of chloride ions into the granule disrupts cationic shielding, le ading to rapid swelling, exocytosis and hydration of mucus. Such a model ex plains the physical-chemical mechanisms involved in mucous granule exocytos is.