Submitted on December 23, 2008
Revised on May 18, 2009
Accepted on May 19, 2009
Differential Regulation of the Renal Sodium/Phosphate Co-Transporters NaPi-IIa, NaPi-IIc and PiT-2 in Dietary Potassium Deficiency
Sophia Y Breusegem1*, Hideaki Takahashi2, Hector Giral-Arnal, Xiaoxin Wang3, Tao Jiang3, Jill W. Verlander4, Paul Wilson3, Shinobu Miyazaki-Anzai3, Eileen Sutherland3, Yupanqui Caldas3, Judith T Blaine, Hiroko Segawa5, Ken-ichi Miyamoto6, Nicholas P Barry3, and Moshe Levi3
1 University of Cambridge
2 Jichi Medical School
3 University of Colorado Denver
4 University of Florida College of Medicine
5 Institution of Health Biosciences, The University of Tokushima Graduate School, Tokushima
6 Tokushima University
* To whom correspondence should be addressed. E-mail: syab2{at}cam.ac.uk.
Dietary potassium (K)-deficiency is accompanied by phosphaturia, and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (Pi) transport activity. We previously showed that K-deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na/Pi co-transporter 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 et al., Kidney Int. 60, 694-704, 2001; Inoue et al., J. Biol. Chem. 279, 49160-49171, 2004). Here we investigated the role of the renal Na/Pi co-transporters 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 Pi 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-llc 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.
