Calcium signaling complexes in microdomains of polarized secretory cells

The highly polarized nature of epithelial cells in exocrine glands necessitates targeting, assembly into complexes and confinement of the molecules comprising the Ca2+ signaling apparatus, to cellular microdomains. Such high degree of polarized localization has been shown for all Ca2+ signaling molecules tested, including G protein coupled receptors and their associated proteins, Ca2+ pumps, Ca2+ influx channels at the plasma membrane and Ca2+ release channels in the endoplasmic reticulum. Although the physiological significance of polarized Ca2+ signaling is clear, little is known about the mechanism of targeting, assembly and retention of Ca2+ signaling complexes in cellular microdomains. The present review attempts to summarize the evidence in favor of polarized expression of Ca2+ signaling proteins at the apical pole of secretory cells with emphasis on the role of scaffolding proteins in the assembly and function of the Ca2+ signaling complexes. The consequence of polarized enrichment of Ca2+ signaling complexes at the apical pole is generation of an apical to basal pole gradient of cell responsiveness that, at low physiological agonist concentrations, limits Ca2+ spikes to the apical pole, and when a Ca2+ wave occurs, it always propagates from the apical to the basal pole. Our understanding of Ca2+ signaling in microdomains is likely to increase rapidly with the application of techniques to controllably and selectively disrupt components of the complexes and apply high resolution recording techniques, such as TIRF microscopy to this problem.