The roles of Na/Pi-II transporters in phosphate metabolism.
The renal type II Na/Pi cotransporters, Na/Pi-IIa and Na/Pi-IIc, are expressed in the brush border membrane (BBM) of the renal proximal tubule cells. Because it has long been thought that Na/Pi-IIa alone can regulate the reabsorption of phosphate in the proximal renal tubules, Na/Pi-IIc has not been paid much attention by the renal research community. Recent studies, however, have identified Na/Pi-IIc mutations as the defective cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). This finding indicates that Na/Pi-IIc has a rather important role in renal Pi reabsorption and bone mineralization, and that it may be a key determinant of plasma Pi concentrations in humans. Studies of Na/Pi-IIc mice indicate that Na/Pi-IIc is necessary for normal calcium homeostasis, but its role in the regulation of Pi metabolism and bone physiology may be different from that in HHRH patients. Of note, Na/Pi-IIc KO mice display abnormal vitamin D regulation without hypophosphatemia or hyperphosphaturia. Thus, Na/Pi-IIc may be involved in regulating renal vitamin D synthesis in the proximal tubular cells. The identification of proteins that interact with Na/Pi-IIc is an important area of future research. The physiologic roles of Na/Pi-IIa and Na/Pi-IIc require future elucidation.
Segawa
Hiroko
H
Department of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School, Kuramoto-Cho 3, Tokushima 770-8503, Japan. segawa@nutr.med.tokushima-u.ac.jp
Aranami
Fumito
F
Kaneko
Ichiro
I
Tomoe
Yuka
Y
Miyamoto
Ken-ichi
K
D000818:Animals; D053098:Familial Hypophosphatemic Rickets / Q000150:complications / Q000378:metabolism; D006801:Humans; D053565:Hypercalciuria / Q000150:complications / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010710:Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D050610:Sodium-Phosphate Cotransporter Proteins, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D010710:Phosphates; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; C093376:sodium-hydrogen exchanger regulatory factor