Polarized calcium and calmodulin signaling in secretory epithelia

This review examines polarized calcium and calmodulin signaling in exocrine epithelial cells. The calcium ion is a simple, evolutionarily ancient, and universal second messenger. In exocrine epithelial cells, it regulates essential functions such as exocytosis, fluid secretion, and gene expression. Exocrine cells are structurally polarized, with the apical region usually dedicated to secretion. Recent advances in technology, in particular the development of videoimaging and confocal microscopy, have led to the discovery of polarized, subcellular calcium signals in these cell types. The properties of a rich variety of local and global calcium signals have now been described in secretory epithelial cells. Secretagogues stimulate apical-to-basal waves of calcium in many exocrine cell types, but there are some interesting exceptions to this rule. The shapes of intracellular calcium signals are determined by the distribution of calcium-releasing channels and mechanisms that limit calcium elevation. Polarized distribution of calcium-handling mechanisms also leads to transcellular calcium transport in exocrine epithelial cells. This transport can deliver considerable amounts of calcium into secreted fluids. Multicellular polarized calcium signals can coordinate the activity of many individual cells in epithelial secretory tissue. Certain particularly sensitive cells serve as pacemakers for initiation of intercellular calcium waves. Many calcium signaling pathways involve activation of calmodulin. This ubiquitous protein regulates secretion in exocrine cells and also activates interesting feedback interactions with calcium channels and transporters. Very recently it became possible to directly study polarized calcium-calmodulin reactions and to visualize the process of hormone-induced redistribution of calmodulin in live cells. The structural and functional polarity of secretory epithelia alongside the polarity of its calcium and calmodulin signaling present an interesting lesson in tissue organization.