New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter.
Abnormalities of the inorganic phosphate (Pi) reabsorption in the kidney result in various metabolic disorders. Na+-dependent Pi (Na/Pi) transporters in the brush border membrane of proximal tubular cells mediate the rate-limiting step in the overall Pi-reabsorptive process. Type IIa and type IIc Na/Pi cotransporters are expressed in the apical membrane of proximal tubular cells and mediate Na/Pi cotransport; the extent of Pi reabsorption in the proximal tubules is determined largely by the abundance of the type IIa Na/Pi cotransporter. However, several studies suggest that the type IIc cotransporter in Pi reabsorption may also play a role in this process. For example, mutation of the type IIc Na/Pi cotransporter gene results in hereditary hypophosphatemic rickets with hypercalciuria, suggesting that the type IIc transporter plays an important role in renal Pi reabsorption in humans and may be a key determinant of the plasma Pi concentration. The type IIc Na/Pi transporter is regulated by parathyroid hormone, dietary Pi, and fibroblast growth factor 23, and studies suggest a differential regulation of the IIa and IIc transporters. Indeed, differences in temporal and/or spatial expression of the type IIa and type IIc Na/Pi transporters may be required for normal phosphate homeostasis and bone development. This review will briefly summarize the regulation of renal Pi transporters in various Pi-wasting disorders and highlight the role of a relatively new member of the Na/Pi cotransporter family: the type IIc Na/Pi transporter/SLC34A3.
Department of Molecular Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan. miyamoto@nutr.med.tokushima-u.ac.jp
Ken-ichi
K
Miyamoto
Mikiko
M
Ito
Sawako
S
Tatsumi
Masashi
M
Kuwahata
Hiroko
H
Segawa
D000042:Absorption; D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000378:metabolism*
D029363:Organic Anion Transporters, Sodium-Dependent; D010710:Phosphates; D020033:Protein Isoforms; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters