• 1
    Murer H, Forster I, Biber J. The sodium phosphate cotransporter family SLC34. Pflugers Arch 2004;447:7637.
  • 2
    Forster IC, Hernando N, Biber J, Murer H. Proximal tubular handling of phosphate: a molecular perspective. Kidney Int 2006;70:154859.
  • 3
    Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 2009;5:6119.
  • 4
    Strom TM, Juppner H. PHEX, FGF23, DMP1 and beyond. Curr Opin Nephrol Hypertens 2008;17:35762.
  • 5
    Berndt T, Thomas LF, Craig TA, Sommer S, Li X, Bergstralh EJ et al. Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption. Proc Natl Acad Sci U S A 2007;104:1108590.
  • 6
    Wagner CA, Biber J, Murer H. What goes in must come out--the small intestine modulates renal phosphate excretion. Nephrol Dial Transplant 2007;22:34112.
  • 7
    Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 2000;80:1373409.
  • 8
    Werner A, Moore ML, Mantei N, Biber J, Semenza G, Murer H. Cloning and expression of cDNA for a Na/Pi cotransport system of kidney cortex. Proc Natl Acad Sci U S A 1991;88:960812.
  • 9
    Custer M, Lotscher M, Biber J, Murer H, Kaissling B. Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry. Am J Physiol 1994;266:F76774.
  • 10
    Custer M, Meier F, Schlatter E, Greger R, Garcia-Perez A, Biber J et al. Localization of NaPi-1, a Na-Pi cotransporter, in rabbit kidney proximal tubules. I. mRNA localization by reverse transcription/polymerase chain reaction. Pflugers Arch 1993;424:2039.
  • 11
    Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H et al. The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Renal Physiol 2009;296:F6919.
  • 12
    Villa-Bellosta R, Sorribas V. Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis. Pflugers Arch 2009;459:499508.
  • 13
    Tenenhouse HS, Roy S, Martel J, Gauthier C. Differential expression, abundance, and regulation of Na+-phosphate cotransporter genes in murine kidney. Am J Physiol 1998;275:F52734.
  • 14
    Jutabha P, Kanai Y, Hosoyamada M, Chairoungdua A, Kim DK, Iribe Y et al. Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule. J Biol Chem 2003;278:279308.
  • 15
    Anzai N, Jutabha P, Kanai Y, Endou H. Integrated physiology of proximal tubular organic anion transport. Curr Opin Nephrol Hypertens 2005;14:4729.
  • 16
    Verri T, Markovich D, Perego C, Norbis F, Stange G, Sorribas V et al. Cloning of a rabbit renal Na-Pi cotransporter, which is regulated by dietary phosphate. Am J Physiol 1995;268:F62633.
  • 17
    Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS. Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci U S A 1998;95:53727.
  • 18
    Wagner CA, Biber J, Murer H. Of men and mice: who is in control of renal phosphate reabsorption? J Am Soc Nephrol 2008;19:16256.
  • 19
    Tenenhouse HS, Martel J, Gauthier C, Segawa H, Miyamoto K. Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol 2003;285:F12718.
  • 20
    Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I et al. Growth-related renal type II Na/Pi cotransporter. J Biol Chem 2002;277:1966572.
  • 21
    Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T et al. Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol 2005;288:F58796.
  • 22
    Segawa H, Yamanaka S, Onitsuka A, Tomoe Y, Kuwahata M, Ito M et al. Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter. Am J Physiol Renal Physiol 2007;292:F395403.
  • 23
    Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 2002;347:98391.
  • 24
    Virkki LV, Forster IC, Hernando N, Biber J, Murer H. Functional characterization of two naturally occurring mutations in the human sodium-phosphate cotransporter type IIa. J Bone Miner Res 2003;18:213541.
  • 25
    Lapointe JY, Tessier J, Paquette Y, Wallendorff B, Coady MJ, Pichette V et al. NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak. Kidney Int 2006;69:22617.
  • 26
    Tieder M, Modai D, Samuel R, Arie R, Halabe A, Bab I et al. Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med 1985;312:6117.
  • 27
    Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 2006;78:17992.
  • 28
    Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 2006;78:193201.
  • 29
    Ichikawa S, Sorenson AH, Imel EA, Friedman NE, Gertner JM, Econs MJ. Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab 2006;91:40227.
  • 30
    Jaureguiberry G, Carpenter TO, Forman S, Juppner H, Bergwitz C. A novel missense mutation in SLC34A3 that causes hereditary hypophosphatemic rickets with hypercalciuria in humans identifies threonine 137 as an important determinant of sodium-phosphate cotransport in NaPi-IIc. Am J Physiol Renal Physiol 2008;295:F3719.
  • 31
    Tencza AL, Ichikawa S, Dang A, Kenagy D, McCarthy E, Econs MJ et al. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab 2009;94:44338.
  • 32
    Ohkido I, Segawa H, Yanagida R, Nakamura M, Miyamoto K. Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney. Pflugers Arch 2003;446:10615.
  • 33
    Segawa H, Onitsuka A, Furutani J, Kaneko I, Aranami F, Matsumoto N et al. Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development. Am J Physiol Renal Physiol 2009;297:F6718.
  • 34
    Keusch I, Traebert M, Lotscher M, Kaissling B, Murer H, Biber J. Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the proximal tubular Na/Pi-cotransporter type II. Kidney Int 1998;54:122432.
  • 35
    Pfister MF, Lederer E, Forgo J, Ziegler U, Lotscher M, Quabius ES et al. Parathyroid hormone-dependent degradation of type II Na+/Pi cotransporters. J Biol Chem 1997;272:2012530.
  • 36
    Kumar R. Tumor-induced osteomalacia and the regulation of phosphate homeostasis. Bone 2000;27:3338.
  • 37
    ADHR-Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 2000;26:3458.
  • 38
    Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K et al. Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 2002;143:317982.
  • 39
    Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 2001;98:65005.
  • 40
    Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T et al. FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem Biophys Res Commun 2004;314:40914.
  • 41
    Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K et al. Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflugers Arch 2003;446:58592.
  • 42
    Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol 2009;297:F28291.
  • 43
    Baum M, Schiavi S, Dwarakanath V, Quigley R. Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules. Kidney Int 2005;68:114853.
  • 44
    Yamashita T, Konishi M, Miyake A, Inui K, Itoh N. Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. J Biol Chem 2002;277:2826570.
  • 45
    Bacic D, Schulz N, Biber J, Kaissling B, Murer H, Wagner CA. Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney. Pflugers Arch 2003;446:5260.
  • 46
    Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M et al. Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol 2007;18:26838.
  • 47
    Saito H, Maeda A, Ohtomo S, Hirata M, Kusano K, Kato S et al. Circulating FGF-23 is regulated by 1alpha,25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem 2005;280:25439.
  • 48
    Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007;117:40038.
  • 49
    Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004;19:42935.
  • 50
    Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: regulation by phosphate? Bone 2004;35:11929.
  • 51
    Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab 2006;291:E3849.
  • 52
    Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006;444:7704.
  • 53
    Xiao L, Naganawa T, Lorenzo J, Carpenter TO, Coffin JD, Hurley MM. Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and klotho. J Biol Chem 2009;285:283446.
  • 54
    Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390:4551.
  • 55
    Farrow EG, Davis SI, Summers LJ, White KE. Initial FGF23-mediated signaling occurs in the distal convoluted tubule. J Am Soc Nephrol 2009;20:95560.
  • 56
    Brownstein CA, Adler F, Nelson-Williams C, Iijima J, Li P, Imura A et al. A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism. Proc Natl Acad Sci U S A 2008;105:345560.
  • 57
    Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Musculoskelet Neuronal Interact 2007;7:3189.
  • 58
    Francis F, Hennig S, Korn B, Reinhardt R, De Jong P, Poustka A et al. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet 1995;11:1306.
  • 59
    Beck L, Soumounou Y, Martel J, Krishnamurthy G, Gauthier C, Goodyer CG et al. Pex/PEX tissue distribution and evidence for a deletion in the 3′ region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest 1997;99:12009.
  • 60
    Tenenhouse HS. X-linked hypophosphataemia: a homologous disorder in humans and mice. Nephrol Dial Transplant 1999;14:33341.
  • 61
    Sabbagh Y, Jones AO, Tenenhouse HS. PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia. Hum Mutat 2000;16:16.
  • 62
    Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R et al. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun 2001;284:97781.
  • 63
    Campos M, Couture C, Hirata IY, Juliano MA, Loisel TP, Crine P et al. Human recombinant endopeptidase PHEX has a strict S1’ specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein. Biochem J 2003;373:2719.
  • 64
    Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD. Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem 2003;278:3741926.
  • 65
    Benet-Pages A, Lorenz-Depiereux B, Zischka H, White KE, Econs MJ, Strom TM. FGF23 is processed by proprotein convertases but not by PHEX. Bone 2004;35:45562.
  • 66
    Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 2004;23:42132.
  • 67
    Yuan B, Takaiwa M, Clemens TL, Feng JQ, Kumar R, Rowe PS et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest 2008;118:72234.
  • 68
    Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 2006;38:13105.
  • 69
    Liu S, Zhou J, Tang W, Menard R, Feng JQ, Quarles LD. Pathogenic role of Fgf23 in Dmp1-null mice. Am J Physiol Endocrinol Metab 2008;295:E25461.
  • 70
    Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L et al. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 2008;359:112835.
  • 71
    Hernando N, Deliot N, Gisler SM, Lederer E, Weinman EJ, Biber J et al. PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters. Proc Natl Acad Sci U S A 2002;99:1195762.
  • 72
    Shenolikar S, Voltz JW, Minkoff CM, Wade JB, Weinman EJ. Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 2002;99:114705.
  • 73
    Villa-Bellosta R, Barac-Nieto M, Breusegem SY, Barry NP, Levi M, Sorribas V. Interactions of the growth-related, type IIc renal sodium/phosphate cotransporter with PDZ proteins. Kidney Int 2008;73:45664.
  • 74
    Markovich D, Verri T, Sorribas V, Forgo J, Biber J, Murer H. Regulation of opossum kidney (OK) cell Na/Pi cotransport by Pi deprivation involves mRNA stability. Pflugers Arch 1995;430:45963.
  • 75
    Martin DR, Ritter CS, Slatopolsky E, Brown AJ. Acute regulation of parathyroid hormone by dietary phosphate. Am J Physiol Endocrinol Metab 2005;289:E72934.