Our lab is interested in hormone-mediated calcium and phosphate transport across the intestine. The combined data of many studies has supported a model system in which these ions are taken up at the brush border by specific transporters and transferred to vesicles. The vesicles are the vectorially transported to the opposite side of the cell along cytoskeletal elements, where exocytosis completes the transport process.
Another interest in our lab is how membrane receptors for the vitamin D metabolites are involved in regulating uptake. The stimulatory metabolite, 1,25(OH)2D3, binds to the 1,25D3-MARRS receptor (PDIA3) at the basal lateral membrane and activates protein kinases A and C. Protein kinase A mediates calcium uptake at the brush border, while protein kinase C stimulates phosphate uptake. Both signal transduction events and uptake of calcium and phosphate uptake occur very rapidly (seconds-minutes), and are sometimes referred to as ‘non-genomic effects’. In addition, we have found that binding of hormone to the 1,25D3-MARRS receptor causes it to be translocated to the nucleus, potentially resulting in regulation of gene expression. Both pathways contribute to the complex response of a cell to a steroid hormone.
The inhibitory metabolite of vitamin D, 24,25(OH)2D3, binds to the enzyme catalase to decrease activity and raise hydrogen peroxide levels. The oxidant in turn, inactivates binding of stimulatory hormone to the 1,25D3-MARRS receptor, as well as inhibiting protein kinase C activity.