Genomes and Genes
Gene Symbol: Slc34a1
Description: solute carrier family 34 member 1
Alias: NaPi-2, NaPi2A, Npt2, Slc17a2, sodium-dependent phosphate transport protein 2A, Na(+)-dependent phosphate cotransporter 2A, Na(+)/Pi cotransporter 2A, naPi-2a, sodium-phosphate co-transporter type II, sodium-phosphate transport protein 2A, sodium/phosphate cotransporter 2A, solute carrier family 17 (sodium/hydrogen exchanger) member 2, solute carrier family 34 (sodium phosphate), member 1, solute carrier family 34 (type II sodium/phosphate cotransporter), member 1
- Lambert G, Forster I, Biber J, Murer H. Cysteine residues and the structure of the rat renal proximal tubular type II sodium phosphate cotransporter (rat NaPi IIa). J Membr Biol. 2000;176:133-41 pubmed..A revised secondary structure is proposed which includes two partially repeated motifs that are connected by disulfide bridges formed between cysteine pairs C306-C334 and C225-C520. ..
- Tanimura A, Yamada F, Saito A, Ito M, Kimura T, Anzai N, et al. Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis. J Med Invest. 2011;58:140-7 pubmed..These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells. ..
- Marks J, Churchill L, Debnam E, Unwin R. Matrix extracellular phosphoglycoprotein inhibits phosphate transport. J Am Soc Nephrol. 2008;19:2313-20 pubmed publisher..Taken together, these findings suggest that MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract. ..
- Kohler K, Forster I, Stange G, Biber J, Murer H. Essential cysteine residues of the type IIa Na+/Pi cotransporter. Pflugers Arch. 2003;446:203-10 pubmed..This confirmed that the MTS reagent site of action was Cys-460 and that modification of native cysteines does not contribute to S460C behavior. ..
- Ohnishi M, Razzaque M. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 2010;24:3562-71 pubmed publisher..Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho(-/-) mice...
- Dobrinskikh E, Giral H, Caldas Y, Levi M, Doctor R. Shank2 redistributes with NaPilla during regulated endocytosis. Am J Physiol Cell Physiol. 2010;299:C1324-34 pubmed publisher..These in vivo findings indicate that Shank2 is positioned to coordinate the regulated endocytic retrieval and downregulation of NaPiIIa in rat renal proximal tubule cells. ..
- Bielesz B, Bacic D, Honegger K, Biber J, Murer H, Wagner C. Unchanged expression of the sodium-dependent phosphate cotransporter NaPi-IIa despite diurnal changes in renal phosphate excretion. Pflugers Arch. 2006;452:683-9 pubmed..Thus, the diurnal changes in urinary phosphate excretion appear to be mainly related to changes in serum phosphate and tubular threshold but not to NaPi-IIa expression. ..
- Xiao L, Naganawa T, Lorenzo J, Carpenter T, Coffin J, Hurley M. Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and KLOTHO. J Biol Chem. 2010;285:2834-46 pubmed publisher..In addition, immunohistochemistry demonstrated co-localization of FGF23 and HMW FGF2 protein in osteoblasts and osteocytes from Hyp mice. This study reveals a novel mechanism of regulation of the FGF23-P(i) homeostatic axis...
- Kamimoto M, Mizuno S, Ohnishi H, Mizuno Horikawa Y. Type 2a sodium-phosphate co-transporter serves as a histological predictor of renal dysfunction and tubular apical damage in the kidneys of septic mice. Biomed Res. 2009;30:251-8 pubmed..Our data indicate that the loss of NaPiT2a is a reliable marker for predicting the progression of septic ARF, while local hypoxia might be involved in the decrease of NaPiT2a expression. ..
- Lanaspa M, Caldas Y, Breusegem S, AndrÃ©s Hernando A, Cicerchi C, Levi M, et al. Inorganic phosphate modulates the expression of the NaPi-2a transporter in the trans-Golgi network and the interaction with PIST in the proximal tubule. Biomed Res Int. 2013;2013:513932 pubmed publisher..Our data supports the view that NaPi-2a is subjected to retrograde trafficking from the plasma membrane to the TGN using one of the machineries involved in endosomal transport and explains the reported expression of NaPi-2a in the TGN. ..
- Sorribas V, Halaihel N, Puttaparthi K, Rogers T, Cronin R, Alcalde A, et al. Gentamicin causes endocytosis of Na/Pi cotransporter protein (NaPi-2). Kidney Int. 2001;59:1024-36 pubmed
- Khan S, Canales B. Ultrastructural investigation of crystal deposits in Npt2a knockout mice: are they similar to human Randall's plaques?. J Urol. 2011;186:1107-13 pubmed publisher..Since Npt2a null mice purge the renal crystal deposits, these mice may serve as a model in which to investigate the elimination of crystal deposits in children and adults with nephrocalcinosis. ..
- Tatsumi S, Miyamoto K, Kouda T, Motonaga K, Katai K, Ohkido I, et al. Identification of three isoforms for the Na+-dependent phosphate cotransporter (NaPi-2) in rat kidney. J Biol Chem. 1998;273:28568-75 pubmed..The results suggest that these short isoforms may function as a dominant negative inhibitor of the full-length transporter. ..
- Matsuzaki H, Katsumata S, Kajita Y, Miwa M. Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats. Magnes Res. 2013;26:83-6 pubmed publisher..These results suggest that Mg deficiency induces downregulation of 1?(OH)ase and type IIa and IIc Na/Pi cotransporters, and upregulation of 24(OH)ase in the kidney. ..
- Wagner C, Waldegger S, Osswald H, Biber J, Murer H, Busch A, et al. Heavy metals inhibit Pi-induced currents through human brush-border NaPi-3 cotransporter in Xenopus oocytes. Am J Physiol. 1996;271:F926-30 pubmed..Heavy metal-mediated inhibition of NaPi-3 may be responsible for the phosphaturia observed after intoxication with these compounds...
- Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson M, 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:F282-91 pubmed publisher..6 +/- 0.3 vs. 5.2 +/- 0.5 mg/dl) or BBM NaPi-2a and NaPi-2c expression. These data show that FGFR1 is the predominant receptor for the hypophosphatemic action of FGF23 in vivo, with FGFR4 likely playing a minor role. ..
- Shiga T, Kimira Y, Mano H, Kawata T, Tadokoro T, Suzuki T, et al. Vitamin Bâ‚â‚‚ deficiency-induced increase of osteoclastic bone resorption caused by abnormal renal resorption of inorganic phosphorus via Napi2a. Biosci Biotechnol Biochem. 2016;80:510-3 pubmed publisher..b>Napi2a, a renal cotransporter for Pi reabsorption, accumulated on plasma membranes in a vitamin B12 deficiency suggests ..
- Ikeda S, Yamamoto H, Masuda M, Takei Y, Nakahashi O, Kozai M, et al. Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation. Am J Physiol Renal Physiol. 2014;306:F744-50 pubmed publisher..These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation. ..
- Sizova D, Velazquez H, Sampaio Maia B, Quelhas Santos J, Pestana M, Desir G. Renalase regulates renal dopamine and phosphate metabolism. Am J Physiol Renal Physiol. 2013;305:F839-44 pubmed publisher..The signal to increase renal DA synthesis is strong since it overcomes a compensatory increase in COMT activity. ..
- Forster I, Traebert M, Jankowski M, Stange G, Biber J, Murer H. Protein kinase C activators induce membrane retrieval of type II Na+-phosphate cotransporters expressed in Xenopus oocytes. J Physiol. 1999;517 ( Pt 2):327-40 pubmed..8. These findings document a specific retrieval of exogenous type II Na+-Pi cotransporters induced by activation of a PKC pathway in the Xenopus oocyte. ..
- Lotscher M, Scarpetta Y, Levi M, Halaihel N, Wang H, Zajicek H, et al. Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement. J Clin Invest. 1999;104:483-94 pubmed
- Murray R, Holthouser K, Clark B, Salyer S, Barati M, Khundmiri S, et al. Parathyroid hormone (PTH) decreases sodium-phosphate cotransporter type IIa (NpT2a) mRNA stability. Am J Physiol Renal Physiol. 2013;304:F1076-85 pubmed publisher..These findings suggest that responses to chronic PTH exposure are selectively regulated at a posttranscriptional level. The persistence of the phosphaturic response to PTH occurs through posttranscriptional mechanisms. ..
- Zeng M, Wang X, Wang X, Zhao X. Effects of phosphonoformic acid and renagel on renal type IIa sodium-dependent phosphate cotransporter mRNA expression in hyperphosphatemia rats. Ren Fail. 2012;34:358-63 pubmed publisher..Renagel can also decrease serum P and upregulate renal NaPi-2 mRNA expression. ..
- Prie D, Torres P, Friedlander G. Phosphate handling: new genes, new molecules. Horm Res Paediatr. 2011;76 Suppl 1:71-5 pubmed publisher..This progress may allow development of new drugs that interfere with phosphate transporters, hormonal receptors or associated proteins to improve treatment and to help prevent secondary hyperparathyroidism. ..
- Chau H, El Maadawy S, McKee M, Tenenhouse H. Renal calcification in mice homozygous for the disrupted type IIa Na/Pi cotransporter gene Npt2. J Bone Miner Res. 2003;18:644-57 pubmedMice homozygous for the disrupted renal type IIa sodium/phosphate (Na/Pi) cotransporter gene (Npt2-/-) exhibit renal Pi wasting, hypophosphatemia, and an adaptive increase in the serum concentration of 1,25-dihydroxyvitamin D with ..
- Moe S, Radcliffe J, White K, Gattone V, Seifert M, Chen X, et al. The pathophysiology of early-stage chronic kidney disease-mineral bone disorder (CKD-MBD) and response to phosphate binders in the rat. J Bone Miner Res. 2011;26:2672-81 pubmed publisher..These results demonstrate marked abnormalities in kidney, intestine, and bone in early CKD-MBD. While phosphate binders were effective in lowering urine phosphorus, they had little effect on end organs after 1 week of administration. ..
- Faroqui S, Levi M, Soleimani M, Amlal H. Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia. Kidney Int. 2008;73:1141-50 pubmed publisher..These effects are independent of food intake or parathyroid hormone levels and likely not mediated through the activation of estrogen receptor alpha subtype. ..
- Xiao Y, Boyer C, Vincent E, Dugré A, Vachon V, Potier M, et al. Involvement of disulphide bonds in the renal sodium/phosphate co-transporter NaPi-2. Biochem J. 1997;323 ( Pt 2):401-8 pubmed
- Ritthaler T, Traebert M, Lotscher M, Biber J, Murer H, Kaissling B. Effects of phosphate intake on distribution of type II Na/Pi cotransporter mRNA in rat kidney. Kidney Int. 1999;55:976-83 pubmed..Thus, the early adaptation to altered Pi intake involves mRNA-independent mechanisms. The up- or down-regulation of NaPi-2 protein abundance in the BBM and NaPi-2 mRNA in PT affects mainly midcortical and superficial nephrons. ..
- Prie D, Couette S, Fernandes I, Silve C, Friedlander G. P-glycoprotein inhibitors stimulate renal phosphate reabsorption in rats. Kidney Int. 2001;60:1069-76 pubmed..protein 1 (MDR1) expressed on the apical membrane of renal proximal tubular cells where the Na-Pi cotransporter (NPT2) is also expressed. We hypothesized that Dip could increase renal Pi reabsorption by inhibiting Pgp activity...
- Lundquist P, Ritchie H, Moore K, Lundgren T, Linde A. Phosphate and calcium uptake by rat odontoblast-like MRPC-1 cells concomitant with mineralization. J Bone Miner Res. 2002;17:1801-13 pubmed
- Hioki H, Fujiyama F, Taki K, Tomioka R, Furuta T, Tamamaki N, et al. Differential distribution of vesicular glutamate transporters in the rat cerebellar cortex. Neuroscience. 2003;117:1-6 pubmed..Thus, it would be the next interesting issue to determine whether mossy-fiber terminals co-expressing VGluT1 and VGluT2 show synaptic facilitation or depression. ..
- Elhalel M, Wald H, Rubinger D, Gal Moscovici A, Inoue M, Levi M, et al. Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure: role of parathyroid hormone (PTH) and dietary phosphate (Pi). Pflugers Arch. 2004;449:265-70 pubmed
- Nakagawa T, Yamaguchi M. Overexpression of regucalcin enhances its nuclear localization and suppresses L-type Ca2+ channel and calcium-sensing receptor mRNA expressions in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem. 2006;99:1064-77 pubmed
- 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;78:193-201 pubmed..Identification of the gene mutated in a further form of hypophosphatemia adds to the understanding of phosphate homeostasis and may help to elucidate the interaction of the proteins involved in this pathway. ..
- Zhang C, Shi L, Li Y, Zhu Q, Jin C, Wang H, et al. Effect of hyperphosphatemia on gene expression of the Na-Pi cotransporter in rats. Genet Mol Res. 2016;14:19404-10 pubmed publisher..05). Hyperphosphatemia significantly affected NaPi-IIa and NaPi-III mRNA expression, and a factor promote an increase in intact parathyroid hormone independently of calcium. ..
- Katai K, Segawa H, Haga H, Morita K, Arai H, Tatsumi S, et al. Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney. J Biochem. 1997;121:50-5 pubmed..These results suggested that rapid endocytotic internalization of NaP(i)-2 may occur specifically in the brush border membrane following an acute increase in dietary P(i) intake. ..
- Kastner C, Pohl M, Sendeski M, Stange G, Wagner C, Jensen B, et al. Effects of receptor-mediated endocytosis and tubular protein composition on volume retention in experimental glomerulonephritis. Am J Physiol Renal Physiol. 2009;296:F902-11 pubmed publisher..Enhanced proteolytic cleavage of ENaC points to a novel mechanism of channel activation which may involve the action of filtered plasma proteases. ..
- Muller D, Houpert P, Cambar J, Henge Napoli M. Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells. Toxicol Appl Pharmacol. 2006;214:166-77 pubmed..Taken together, these data suggest that the cytotoxic fraction of uranium is a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate co-transporter system...
- Radanovic T, Gisler S, Biber J, Murer H. Topology of the type IIa Na+/P(i) cotransporter. J Membr Biol. 2006;212:41-9 pubmed..The proposed model is in good agreement with the prediction of the NaPi-IIa structure obtained by the hidden Markov algorithm HMMTOP. ..
- Villa Bellosta R, Sorribas V. Arsenate transport by sodium/phosphate cotransporter type IIb. Toxicol Appl Pharmacol. 2010;247:36-40 pubmed publisher..7 microM), which are very similar to the affinities for Pi. Therefore, NaPiIIb can have a prominent role in the toxicokinetics of arsenic following oral exposure to freshwater or food contaminated with As(V). ..
- McHaffie G, Graham C, Kohl B, Strunck Warnecke U, Werner A. The role of an intracellular cysteine stretch in the sorting of the type II Na/phosphate cotransporter. Biochim Biophys Acta. 2007;1768:2099-106 pubmed..Our results suggest that the modified cysteine motif prevents the constructs from basolateral sorting. Additional sorting determinants located downstream of the cysteine stretch may release the cargo to the apical compartment. ..
- Lotscher M, Kaissling B, Biber J, Murer H, Kempson S, Levi M. Regulation of rat renal Na/Pi-cotransporter by parathyroid hormone: immunohistochemistry. Kidney Int. 1996;49:1010-1 pubmed
- Nakatani T, Sarraj B, Ohnishi M, Densmore M, Taguchi T, Goetz R, et al. In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis. FASEB J. 2009;23:433-41 pubmed publisher..Together, these results provide compelling evidence that Fgf23 does not have a klotho-independent role in the regulation of systemic phosphate and vitamin D homeostasis. ..
- McWilliams R, Breusegem S, Brodsky K, Kim E, Levi M, Doctor R. Shank2E binds NaP(i) cotransporter at the apical membrane of proximal tubule cells. Am J Physiol Cell Physiol. 2005;289:C1042-51 pubmed..In sum, Shank2E is concentrated in the apical domain of renal PT cells, specifically binds NaP(i)-IIa via PDZ interactions, and undergoes P(i)-induced internalization. ..
- Khan S, Glenton P. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter. Am J Physiol Renal Physiol. 2008;294:F1109-15 pubmed publisher..The absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis. ..
- Lambert G, Traebert M, Biber J, Murer H. Cleavage of disulfide bonds leads to inactivation and degradation of the type IIa, but not type IIb sodium phosphate cotransporter expressed in Xenopus laevis oocytes. J Membr Biol. 2000;176:143-9 pubmed..Sequence comparisons suggest the involvement/presence of different disulfide bonds in type IIa and type IIb Na/P(i)-cotransporters. ..
- Nowik M, Picard N, Stange G, Capuano P, Tenenhouse H, Biber J, et al. Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption. Pflugers Arch. 2008;457:539-49 pubmed publisher..Two Na(+)-dependent phosphate transporters, NaPi-IIa (Slc34a1) and NaPi-IIc (Slc34a3), are located in the brush border membrane (BBM) of the proximal tubule and mediate renal ..
- Thumfart J, Jung S, Amasheh S, Kramer S, Peters H, Sommer K, et al. Magnesium stimulates renal phosphate reabsorption. Am J Physiol Renal Physiol. 2008;295:F1126-33 pubmed publisher..Under a high-Mg2+ diet, NaPi-IIa expression is dependent on PTH levels, whereas NaPi-IIc expression seems to be independent of PTH levels. ..
- Burris D, Webster R, Sheriff S, Faroqui R, Levi M, Hawse J, et al. Estrogen directly and specifically downregulates NaPi-IIa through the activation of both estrogen receptor isoforms (ERÎ± and ERÎ²) in rat kidney proximal tubule. Am J Physiol Renal Physiol. 2015;308:F522-34 pubmed publisher..This effect is mediated via a mechanism involving coactivation of both ERÎ± and ERÎ², which likely form a functional heterodimer complex in the rat kidney proximal tubule. ..
- Dërmaku Sopjani M, Sopjani M, Saxena A, Shojaiefard M, Bogatikov E, Alesutan I, et al. Downregulation of NaPi-IIa and NaPi-IIb Na-coupled phosphate transporters by coexpression of Klotho. Cell Physiol Biochem. 2011;28:251-8 pubmed publisher..Treatment of NaPi-IIa- or NaPi-IIb-expressing oocytes with Klotho protein similarly decreased Ip. In conclusion, Klotho down regulates both, renal (NaPi-IIa) and intestinal (NaPi-IIb) phosphate transporters. ..