期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 285, 期 6, 页码 F1225-F1232出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00215.2003
关键词
renal electrolyte transport; PDZ adaptor proteins; mouse; gene deletion; phosphate metabolism
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK055881, R01DK032839] Funding Source: NIH RePORTER
- NIDDK NIH HHS [DK 55881, DK 32839] Funding Source: Medline
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 wildtype 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.
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