Role of megalin, a proximal tubular endocytic receptor, in calcium and phosphate homeostasis.

Megalin is expressed at the apical membranes of proximal tubule cells, acting as an endocytic receptor for a variety of ligands filtered by glomeruli. Megalin, also known as a Ca(2+)-binding receptor, is thought to be involved in systemic and intrarenal calcium and phosphate homeostasis. The complex of 25(OH)D(3) and vitamin D-binding protein is endocytosed via megalin into proximal tubule cells, leading to the activation of 25(OH)D(3) to 1, 25(OH)D(3) in the cells. Megalin knockout mice revealed impaired osteogenesis due to vitamin D deficiency. Megalin is also involved in the metabolism of parathyroid hormone and the regulation of the sodium phosphate cotransporter NaPi-IIa. Decreased expression of megalin may be associated with the pathogenesis of hyperphosphaturia observed in patients with Dent's disease. Further studies will elucidate more detailed roles of megalin in pathological states and the mechanisms for interacting with other molecules for the endocytic functions.