NHERF-1 is required for renal adaptation to a low-phosphate diet.
The sodium-dependent renal phosphate transporter (Npt2, Na-Pi IIa) is the major regulated phosphate transporter in the renal proximal convoluted tubule. Npt2 associates with a number of PDZ-containing proteins including Na+H+ exchanger regulatory factor-1 (NHERF-1). To determine whether NHERF-1 is involved in the acute regulation of phosphate transport, wild-type and NHERF-1 (-/-) mice were stabilized on a high-phosphate diet and then acutely changed to a low-phosphate diet. At 24 h after the change to a low-phosphate diet, there was a significant decrease in the urinary excretion of phosphate in both groups but the urinary excretion of phosphate in NHERF-1 (-/-) mice was significantly higher than in wild-type animals (1,097 +/- 356 vs. 255 +/- 54 ng/min, P < 0.05). Renal mRNA levels and total cellular Npt2 protein did not differ between the animal groups or in response to the changes in diet. Renal brush-border membrane (BBM) expression of Npt2 protein, however, was lower in NHERF-1 (-/-) mice compared with wild-type. In addition, with both the high- and low-phosphate diets, there was increased detection of Npt2 in submicrovillar domains that were particularly prominent in NHERF-1 (-/-) mice compared with wild-type animals. On the other hand, a change from a low-phosphate diet to a high-phosphate diet was associated with a similar increase in the urinary excretion of phosphate in wild-type and NHERF-1 (-/-) animals. These experiments demonstrate that full renal adaptation to a low-phosphate diet requires NHERF-1, which serves to increase BBM expression of Npt2.
Weinman
Edward J
EJ
Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Rm. N3W143, UHM, 22 South Greene Street, Baltimore, MD 21201, USA. eweinman@medicine.umaryland.edu
Boddeti
Anuradha
A
Cunningham
Rochelle
R
Akom
Michael
M
Wang
Fengying
F
Wang
Yu
Y
Liu
Jie
J
Steplock
Deborah
D
Shenolikar
Shirish
S
Wade
James B
JB
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D004032:Diet; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters / Q000378:metabolism
D010710:Phosphates; D010750:Phosphoproteins; D012333:RNA, Messenger; C493549:Slc17a2 protein, mouse; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; C093376:sodium-hydrogen exchanger regulatory factor