Transcellular calcium transport in mammary epithelial cells

The time-honored paradigm for mammary gland transepithelial calcium transport into milk is centered on the view that most, if not all, calcium enters milk through the secretory pathway, and no ionic calcium directly crosses the apical plasma membrane. Data from several recent studies all strongly suggest that most calcium, in fact, is extruded across the apical plasma membrane directly by the plasma membrane calcium-ATPase isoform 2 (PMCA2). In this review we break down transcellular calcium transport into the tasks of calcium entry, calcium sequestration and compartmentalization, and calcium extrusion. We compare and contrast the steps of calcium transport into milk by mammary epithelial cells, and the specific molecules that might perform these tasks, with well-characterized calcium transport mechanisms in other epithelia, such as the kidney, small intestine, and salivary gland. Finally, we suggest an updated model for calcium transport into milk that incorporates calcium transport across the apical plasma membrane.