Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency.

Abstract

Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (P(i)) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-P(i) cotransporter NaPi-IIa, but that the activity, diffusion, and clustering of NaPi-IIa could be modulated by the altered lipid composition of the K-deficient BBM (Zajicek HK, Wang H, Puttaparthi K, Halaihel N, Markovich D, Shayman J, Beliveau R, Wilson P, Rogers T, Levi M. Kidney Int 60: 694-704, 2001; Inoue M, Digman MA, Cheng M, Breusegem SY, Halaihel N, Sorribas V, Mantulin WW, Gratton E, Barry NP, Levi M. J Biol Chem 279: 49160-49171, 2004). Here we investigated the role of the renal Na-P(i) cotransporters NaPi-IIc and PiT-2 in K deficiency. Using Western blotting, immunofluorescence, and quantitative real-time PCR, we found that, in rats and in mice, K deficiency is associated with a dramatic decrease in the NaPi-IIc protein abundance in proximal tubular BBM and in NaPi-IIc mRNA. In addition, we documented the presence of a third Na-coupled P(i) transporter in the renal BBM, PiT-2, whose abundance is also decreased by dietary K deficiency in rats and in mice. Finally, electron microscopy showed subcellular redistribution of NaPi-IIc in K deficiency: in control rats, NaPi-IIc immunolabel was primarily in BBM microvilli, whereas, in K-deficient rats, NaPi-IIc BBM label was reduced, and immunolabel was prevalent in cytoplasmic vesicles. In summary, our results demonstrate that decreases in BBM abundance of the phosphate transporter NaPi-IIc and also PiT-2 might contribute to the phosphaturia of dietary K deficiency, and that the three renal BBM phosphate transporters characterized so far can be differentially regulated by dietary perturbations.

• Authors: Sophia Y Breusegem, Hideaki Takahashi, Hector Giral-Arnal, Xiaoxin Wang, Tao Jiang, Jill W Verlander, Paul Wilson, Shinobu Miyazaki-Anzai, Eileen Sutherland, Yupanqui Caldas, Judith T Blaine, Hiroko Segawa, Ken-ichi Miyamoto, Nicholas P Barry, Moshe Levi
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 297 Issue 2 Pg. F350-61 (Aug 2009) ISSN: 1522-1466 [Electronic] United States
• PMID: 19493963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphorus, Dietary
• RNA, Messenger
• Slc20a2 protein, mouse
• Slc20a2 protein, rat
• Slc34a1 protein, mouse
• Slc34a1 protein, rat
• Slc34a3 protein, mouse
• Slc34a3 protein, rat
• Sodium-Phosphate Cotransporter Proteins, Type III
• Sodium-Phosphate Cotransporter Proteins, Type IIa
• Sodium-Phosphate Cotransporter Proteins, Type IIc

Topics

• Animals
• Biological Transport
• Cell Membrane (metabolism)
• Cytoplasmic Vesicles (metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Hypophosphatemia (metabolism)
• Kidney (metabolism, ultrastructure)
• Male
• Mice
• Mice, Inbred C57BL
• Microvilli (metabolism)
• Phosphorus, Dietary (blood, metabolism, urine)
• Potassium Deficiency (genetics, metabolism)
• Protein Transport
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium-Phosphate Cotransporter Proteins, Type III (genetics, metabolism)
• Sodium-Phosphate Cotransporter Proteins, Type IIa (genetics, metabolism)
• Sodium-Phosphate Cotransporter Proteins, Type IIc (genetics, metabolism)