Cellular/molecular control of renal Na/Pi-cotransport.
A type II Na/Pi-cotransporter located in the brush border membrane is the rate limiting and physiologically regulated step in proximal tubular phosphate (Pi) reabsorption. In states of altered Pi-reabsorption [for example, in response to parathyroid hormone (PTH) and to altered dietary intake of Pi or as a consequence of genetic abnormalities], brush border expression of the type II Na/Pi-cotransporter is accordingly modified. PTH initiates a regulatory cascade leading to membrane retrieval, followed by lysosomal degradation of this transporter; recovery from inhibition requires its de novo synthesis. Pi-deprivation leads to an increased brush border expression of transporters that does not appear to require de novo synthesis in the short term. Pi-overload leads to membrane retrieval and degradation of transporters. Finally, in animals with genetically altered Pi-handling (Hyp; Gy) the brush border membrane expression of the type II Na/Pi-cotransporter is also reduced, suggesting that a genetically altered protein (such as PEX in Hyp) controls the expression of this transporter.
Murer
H
H
Institute of Physiology, Switzerland Physiologisches Institut, Zürich, Switzerland. murer@physiol.unizh.ch
Forster
I
I
Hilfiker
H
H
Pfister
M
M
Kaissling
B
B
Lötscher
M
M
Biber
J
J
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D012964:Sodium