type iia sodium phosphate cotransporter proteins


Summary: An electrogenic sodium-dependent phosphate transporter. It is present primarily in BRUSH BORDER membranes of PROXIMAL RENAL TUBULES.

Top Publications

  1. Biber J, Hernando N, Forster I, Murer H. Regulation of phosphate transport in proximal tubules. Pflugers Arch. 2009;458:39-52 pubmed publisher
    ..The regulatory mechanisms involve various signaling pathways and a number of proteins that interact with Na(+)/P(i) cotransporters. ..
  2. 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. ..
  3. Carlile M, Swan D, Jackson K, Preston Fayers K, Ballester B, Flicek P, et al. Strand selective generation of endo-siRNAs from the Na/phosphate transporter gene Slc34a1 in murine tissues. Nucleic Acids Res. 2009;37:2274-82 pubmed publisher
    ..Significant correlation between random imprinting and antisense transcription could indeed be established. Our findings suggest a novel, more general role for NATs in gene regulation. ..
  4. Mohebbi N, Mihailova M, Wagner C. The calcineurin inhibitor FK506 (tacrolimus) is associated with transient metabolic acidosis and altered expression of renal acid-base transport proteins. Am J Physiol Renal Physiol. 2009;297:F499-509 pubmed publisher
    ..These data suggest that FK506 impacts on several major acid-base transport proteins in the kidney, and its use is associated with transient metabolic acidosis and altered expression of key renal acid-base transport proteins...
  5. Aranami F, Segawa H, Furutani J, Kuwahara S, Tominaga R, Hanabusa E, et al. Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium. J Med Invest. 2010;57:95-108 pubmed
    ..The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. ..
  6. Nakatani T, Ohnishi M, Razzaque M. Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic (Hyp) mouse model. FASEB J. 2009;23:3702-11 pubmed publisher
    ..Our in vivo observations have significant clinical implications in diseases associated with increased FGF23 activity and suggest that the functions of FGF23 can be therapeutically modulated by manipulating the effects of klotho. ..
  7. Farrow E, Summers L, Schiavi S, McCormick J, Ellison D, White K. Altered renal FGF23-mediated activity involving MAPK and Wnt: effects of the Hyp mutation. J Endocrinol. 2010;207:67-75 pubmed publisher
    ..Finally, the current treatment of phosphate and calcitriol for hypophosphatemic disorders may increase FGF23 activity. ..
  8. Blaine J, Okamura K, Giral H, Breusegem S, Caldas Y, Millard A, et al. PTH-induced internalization of apical membrane NaPi2a: role of actin and myosin VI. Am J Physiol Cell Physiol. 2009;297:C1339-46 pubmed publisher
    ..In addition, we demonstrate that a myosin motor that has previously been shown to be coregulated with NaPi2a, myosin VI, is necessary for PTH-induced removal of NaPi2a from BBM microvilli. ..
  9. Xu C, Jin H, Chung Y, Shin J, Hwang S, Kwon J, et al. Low dietary inorganic phosphate affects the lung growth of developing mice. J Vet Sci. 2009;10:105-13 pubmed
    ..These results suggest that optimally regulating Pi consumption may be important to maintain health. ..

More Information


  1. Breusegem S, Takahashi H, Giral Arnal H, Wang X, Jiang T, Verlander J, et al. Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency. Am J Physiol Renal Physiol. 2009;297:F350-61 pubmed publisher
  2. Weinman E, Biswas R, Steplock D, Douglass T, Cunningham R, Shenolikar S. Sodium-hydrogen exchanger regulatory factor 1 (NHERF-1) transduces signals that mediate dopamine inhibition of sodium-phosphate co-transport in mouse kidney. J Biol Chem. 2010;285:13454-60 pubmed publisher
    ..These studies suggest a novel role for the PDZ adapter protein NHERF-1 in coordinating dopamine signals that inhibit renal phosphate transport. ..
  3. Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, et al. Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem. 2010;285:13045-56 pubmed publisher
    ..Renal Sirt1 can be a potential therapeutic target for the treatment of AKI. ..
  4. Kestenbaum B, Glazer N, Köttgen A, Felix J, Hwang S, Liu Y, et al. Common genetic variants associate with serum phosphorus concentration. J Am Soc Nephrol. 2010;21:1223-32 pubmed publisher
    ..05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation. ..
  5. Guttmann Rubinstein L, Lichtstein D, Ilani A, Gal Moscovici A, Scherzer P, Rubinger D. Evidence of a parathyroid hormone-independent chronic effect of estrogen on renal phosphate handling and sodium-dependent phosphate cotransporter type IIa expression. Horm Metab Res. 2010;42:230-6 pubmed publisher
    ..These results suggest that chronic estrogen treatment is associated with an inhibitory, PTH-independent effect on the expression of NaPiIIa in the kidney, leading to sex-related differences in phosphate balance. ..
  6. Tomoe Y, Segawa H, Shiozawa K, Kaneko I, Tominaga R, Hanabusa E, et al. Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice. Am J Physiol Renal Physiol. 2010;298:F1341-50 pubmed publisher
    ..These findings suggest that Npt2a, Npt2c, and PiT-2 are necessary for the phosphaturic activity of FGF23. Thus complementary regulation of Npt2 family proteins may be involved in systemic P(i) homeostasis. ..
  7. Reining S, Liesegang A, Betz H, Biber J, Murer H, Hernando N. Expression of renal and intestinal Na/Pi cotransporters in the absence of GABARAP. Pflugers Arch. 2010;460:207-17 pubmed publisher
    ..However, in response to low Pi diets, the upregulation of NaPi-IIa is greater in the mutant mice. Thus, both the basal expression and the dietary-induced upregulation of NaPi-IIa are increased in the absence of GABARAP. ..
  8. Ishiguro M, Yamamoto H, Masuda M, Kozai M, Takei Y, Tanaka S, et al. Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene. Biochem J. 2010;427:161-9 pubmed publisher
    ..These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner. ..
  9. Weinman E, Steplock D, Zhang Y, Biswas R, Bloch R, Shenolikar S. Cooperativity between the phosphorylation of Thr95 and Ser77 of NHERF-1 in the hormonal regulation of renal phosphate transport. J Biol Chem. 2010;285:25134-8 pubmed publisher
    ..The phosphorylation of Thr(95) facilitates the phosphorylation of Ser(77). This, in turn, results in the dissociation of NHERF-1 from Npt2a and a decrease in phosphate transport in renal proximal tubule cells. ..
  10. 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:F671-8 pubmed publisher
    ..A high-P(i) diet after weaning rescued plasma phosphate levels and the bone phenotype in DKO mice. Our findings thus showed in mice that Npt2a and Npt2c have independent roles in the regulation of plasma P(i) and bone mineralization. ..
  11. Villa Bellosta R, Sorribas V. Different effects of arsenate and phosphonoformate on P(i) transport adaptation in opossum kidney cells. Am J Physiol Cell Physiol. 2009;297:C516-25 pubmed publisher
    ..To conclude, a mathematical definition of the adaptation process is reported, thereby explaining the limited changes in P(i) transport V(max)...
  12. 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. ..
  13. Reining S, Gisler S, Fuster D, Moe O, O Sullivan G, Betz H, et al. GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes. Am J Physiol Renal Physiol. 2009;296:F1118-28 pubmed publisher
    ..The absence of GABARAP does not interfere with the regulation of the cotransporter by either parathyroid hormone or acute changes of dietary P(i) content. ..
  14. Picard N, Capuano P, Stange G, Mihailova M, Kaissling B, Murer H, et al. Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters. Pflugers Arch. 2010;460:677-87 pubmed publisher
    ..Pit-2 protein abundance was also significantly reduced by PTH. Thus, function and expression of BBM phosphate cotransporters are differentially regulated allowing for fine-tuning of renal phosphate reabsorption. ..
  15. Masuda M, Yamamoto H, Kozai M, Tanaka S, Ishiguro M, Takei Y, et al. Regulation of renal sodium-dependent phosphate co-transporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors. Biochem J. 2010;429:583-92 pubmed publisher
    ..In summary, we conclude that VAD induces hyperphosphaturia through the down-regulation of Npt2a and Npt2c gene expression in the kidney. ..
  16. Ito M, Sakurai A, Hayashi K, Ohi A, Kangawa N, Nishiyama T, et al. An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells. Am J Physiol Renal Physiol. 2010;299:F243-54 pubmed publisher
    ..We conclude that targeting of NaPi-IIc to the apical cell surface is regulated by a unique amino acid motif in the cytoplasmic C-terminal domain. ..
  17. Lorenz Depiereux B, Schnabel D, Tiosano D, Häusler G, Strom T. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010;86:267-72 pubmed publisher
    ..Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization. ..
  18. Kempe D, Dërmaku Sopjani M, Fröhlich H, Sopjani M, Umbach A, Puchchakayala G, et al. Rapamycin-induced phosphaturia. Nephrol Dial Transplant. 2010;25:2938-44 pubmed publisher
    ..The present study was performed to elucidate whether mTOR similarly regulates the major renal tubular phosphate transporter NaPi-IIa...
  19. Magen D, Berger L, Coady M, Ilivitzki A, Militianu D, Tieder M, et al. A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome. N Engl J Med. 2010;362:1102-9 pubmed publisher
    ..These findings show that disruption of the human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function and provide evidence of the critical role of NaPi-IIa in human renal phosphate handling. ..
  20. Ohnishi M, Nakatani T, Lanske B, Razzaque M. In vivo genetic evidence for suppressing vascular and soft-tissue calcification through the reduction of serum phosphate levels, even in the presence of high serum calcium and 1,25-dihydroxyvitamin d levels. Circ Cardiovasc Genet. 2009;2:583-90 pubmed publisher
    ..These in vivo observations have significant clinical importance and therapeutic implications for patients with chronic kidney disease with cardiovascular calcification. ..
  21. Weinman E, Steplock D, Cha B, Kovbasnjuk O, Frost N, Cunningham R, et al. PTH transiently increases the percent mobile fraction of Npt2a in OK cells as determined by FRAP. Am J Physiol Renal Physiol. 2009;297:F1560-5 pubmed publisher
    ..Treatment with PTH, presumably by dissociating NHERF-1/Npt2a complexes, transiently increases the mobility of Npt2a, suggesting that freeing of Npt2a from the cytoskeleton precedes PTH-mediated endocytosis. ..
  22. 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. ..
  23. Ohnishi M, Razzaque M. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 2010;24:3562-71 pubmed publisher
    ..The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging. ..
  24. Hu M, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J. 2010;24:3438-50 pubmed publisher
  25. Kempe D, Ackermann T, Boini K, Klaus F, Umbach A, Dërmaku Sopjani M, et al. Akt2/PKBbeta-sensitive regulation of renal phosphate transport. Acta Physiol (Oxf). 2010;200:75-85 pubmed publisher
    ..Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone. ..
  26. 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...
  27. Miedlich S, Zhu E, Sabbagh Y, Demay M. The receptor-dependent actions of 1,25-dihydroxyvitamin D are required for normal growth plate maturation in NPt2a knockout mice. Endocrinology. 2010;151:4607-12 pubmed publisher
    ..These studies demonstrate that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a normal growth plate phenotype in the Npt2a null mice. ..