title: 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.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA. syab2@cam.ac.uk
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Breusegem
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hector
authors.initials: H
authors.lastname: Giral-Arnal
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.forename: Paul
authors.initials: P
authors.lastname: Wilson
authors.forename: Shinobu
authors.initials: S
authors.lastname: Miyazaki-Anzai
authors.forename: Eileen
authors.initials: E
authors.lastname: Sutherland
authors.forename: Yupanqui
authors.initials: Y
authors.lastname: Caldas
authors.forename: Judith T
authors.initials: JT
authors.lastname: Blaine
authors.forename: Hiroko
authors.initials: H
authors.lastname: Segawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Barry
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D017674:Hypophosphatemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011191:Potassium Deficiency / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism*; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000235:genetics / Q000378:metabolism*
chemical_list: D016226:Phosphorus, Dietary; D012333:RNA, Messenger; C493565:Slc20a2 protein, mouse; C493566:Slc20a2 protein, rat; C493555:Slc34a1 protein, mouse; C493556:Slc34a1 protein, rat; C493563:Slc34a3 protein, mouse; C493564:Slc34a3 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc