Skip to main content

Advertisement

Log in

The sodium phosphate cotransporter family SLC34

  • The ABC of Solute Carriers
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

This review summarizes the characteristics of the solute carrier family SLC34 that is represented by the type ll Na/Pi-cotransporters NaPi-lla (SLC34A1), NaPi-llb (SLC34A2) and NaPi-llc (SLC34A3). Other Na/Pi-cotransporters are described within the SLC17 and SLC20 families. Type ll Na/Pi-cotransporters are expressed in several tissues and play a major role in the homeostasis of inorganic phosphate. In kidney and small intestine, type ll Na/Pi-cotransporters are located at the apical sites of epithelial cells and represent the rate limiting steps for transepithelial movement of phosphate. Physiological and pathophysiological regulation of renal and small intestinal epithelial transport of phosphate occurs through alterations in the abundance of type ll Na/Pi-cotransporters.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. Arima K, Hines ER, Kiela PR, Drees JB, Collins JF, Ghishan FK (2002) Glucocorticoid regulation and glycosylation of mouse intestinal type llb Na-Pi cotransporter during ontogeny. Am J Physiol 283:G426–G434

    CAS  Google Scholar 

  2. Bacic D, Hernando N, Traebert M, Lederer E, Völkl H, Biber J, Kaissling B, Murer H (2001) Regulation of the renal type ll Na/Pi-cotransporter by cGMP. Pflugers Arch 442:782–790

    PubMed  Google Scholar 

  3. Bacic D, Schulz N, Biber J, Kaissling B, Murer H, Wagner CA (2003) Involvement of the MAPK-kinase pathway in the PTH mediated regulation of the proximal tubule type ll Na/Pi-cotransporter in mouse kidney. Pflugers Arch 446:52–60

    Google Scholar 

  4. Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS (1998) Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria and skeletal abnormalities. Proc Natl Acad Sci USA 95:5372–5377

    CAS  PubMed  Google Scholar 

  5. Cross HS, Debiec H, Peterlik M (1990) Mechanism and regulation of intestinal phosphate absorption. Miner Electrolyte Metab 16:115–124

    CAS  PubMed  Google Scholar 

  6. Custer M, Lötscher M, Biber J, Murer H, Kaissling B (1994) Expression of Na/Pi cotransport in rat kidney: localization by RT-PCR and immunohistochemistry. Am J Physiol 266: F767–F774

    CAS  PubMed  Google Scholar 

  7. De la Horra C, Hernando N, Lambert G, Forster I, Biber J, Murer H (2000) Molecular determinants of pH sensitivity of the type lla Na/Pi-cotransporter. J Biol Chem 275:6284–6287

    PubMed  Google Scholar 

  8. Field JA, Zhang L, Brun KA, Brooks DP, Edwards RM (1999) Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem Biophys Res Commun 258:578–582

    PubMed  Google Scholar 

  9. Forster IC, Loo DDF, Eskandari S (1999) Stoichiometry and Na+-binding cooperativity of rat and flounder renal type II Na+-Pi-cotransporters. Am J Physiol 276:F644–F649

    CAS  PubMed  Google Scholar 

  10. Forster IC, Köhler K, Biber J, Murer H (2002) Forging the link between structure and function of electrogenic cotransporters: the renal type lla Na/Pi cotransporter as a case study. Prog Biophys Mol Biol 80:69–108

    Article  CAS  PubMed  Google Scholar 

  11. Fukumoto S, Yamashita T (2002) Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens 11:385–389

    PubMed  Google Scholar 

  12. Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H (2001) Interaction of the type IIa Na/Pi-cotransporter with PDZ proteins. J Biol Chem 276:9206–9213

    CAS  PubMed  Google Scholar 

  13. Gupta A, Guo XL, Alvarez UM, Hruska KA (1997) Regulation of sodium-dependent phosphate transport in osteoclasts. J Clin Invest 100:538–548

    CAS  PubMed  Google Scholar 

  14. Hattenhauer O, Traebert M, Murer H, Biber J (1999) Regulation of small intestinal Na-phosphate cotransporter (NaPi type IIb) by dietary phosphate intake. Am J Physiol 277:G756–G762

    CAS  PubMed  Google Scholar 

  15. Hernando N, Deliot N, Gisler S, Lederer E, Weinman EJ, Biber J, Murer H (2002) PDZ-domain interactions and apical expression of type lla Na/Pi-cotransporters. Proc Natl Acad Sci USA 99:11957–11692

    CAS  PubMed  Google Scholar 

  16. Hilfiker H, Hattenhauer O, Traebert M, Forster I., Murer H, Biber J (1998) Characterization of a new murine type II sodium-phosphate cotransporter expressed in mammalian small intestine. Proc Natl Acad Sci USA 95:14564–14569

    CAS  PubMed  Google Scholar 

  17. Hisano S, Haga H, Li Z, Tatsumi S, Miyamoto KI, Takeda E, Fukuui Y (1997) Immunohistochemical and RT-PCR detection of Na-dependent inorganic phosphate cotransporter (NaPi-2) in rat brain. Brain Res 772:149–155

    CAS  PubMed  Google Scholar 

  18. Karim-Jimenez Z, Hernando N, Biber J Murer H (2001) Molecular determinants for apical expression of the renal type IIa NaPi-cotransporter. Pflugers Arch 442:782–790

    PubMed  Google Scholar 

  19. Katai K, Miyamoto KI, Kishida S, Segawa H, Nii T, Tanaka H, Tani Y, Arai H, Tatsumi S, Morita K, Taketani Y, Takeda E (1999) Regulation of intestinal Na-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3. Biochem J 343:705–712

    CAS  PubMed  Google Scholar 

  20. Keusch I, Traebert M, Lötscher M, Kaissling B, Murer H, Biber J (1998) Parathyroid hormone and dietary phosphate provoke lysosomal routing of the proximal tubular Na/Pi-cotransporter type II. Kidney Int 54:1224–1232

    CAS  PubMed  Google Scholar 

  21. Kilav R, Silver J, Biber J, Murer H, Naveh-Many T (1995) Coordinate regulation of rat renal parathyroid hormone receptor mRNA and Na-Pi cotransporter mRNA and protein. Am J Physiol 268:F1017–F1022

    CAS  PubMed  Google Scholar 

  22. Kocher O, Pal R, Roberts M, Cirovic C, Gilchrist A (2003) Targeted disruption of the PDZK1 gene by homologous recombination. Mol Cell Biol 23:1175–1180

    CAS  PubMed  Google Scholar 

  23. Köhler K, Forster IC, Lambert G, Biber J, Murer H (2000) The functional unit of the renal type IIa Na+/Pi cotransporter is a monomer. J Biol Chem 275:26113–26120

    Article  CAS  PubMed  Google Scholar 

  24. Köhler K, Forster IC, Stange G, Biber J Murer H (2002) Identification of functionally important sites in the first intracellular loop of the Na/Pi-IIa cotransporter. Am J Physiol 282: F687–F696

    CAS  Google Scholar 

  25. Kumar R (2002) New insights into phosphate homeostasis: fibroblast growth factor 23 and frizzled-related protein-4 are phosphaturic factors derived from tumors associated with osteomalacia. Curr Opin Nephrol Hypertens 11:547–553

    PubMed  Google Scholar 

  26. Lambert G, Traebert M, Hernando N, Biber J Murer H (1999) Studies on the topology of the renal type II NaPi-cotransporter. Eur J Physiol 437:972–978

    CAS  Google Scholar 

  27. Levi M, Kempson SA, Lötscher M, Biber J, Murer H (1996) Molecular regulation of renal phosphate transport. J Membr Biol 154:1–9

    CAS  PubMed  Google Scholar 

  28. Lötscher M, Scarpetta Y, Levi M, Wang H, Zajicek HK, Biber J, Murer H, Kaissling B (1999) Rapid downregulation of rat renal Na/Pi-cotransporter in response to parathyroid hormone: role of microtubule rearrangement. J Clin Invest 104:483–494

    PubMed  Google Scholar 

  29. Madsen KL, Tavernini MM, Yachimec C, Mendrick DL, Alfonso PJ, Buergin M, Olsen HS, Antonaccio MJ, Thomson ABR, Fedorak RN (1998) Stanniocalcin: a novel protein regulating calcium and phosphate transport across mammalian intestine. Am J Physiol 274:G96–G102

    CAS  PubMed  Google Scholar 

  30. Magagnin S, Werner A, Markovich D, Sorribas V, Stange G, Biber J, Murer H (1993) Expression cloning of human and rat renal cortex Na/Pi-cotransport. Proc Natl Acad Sci USA 90:5979–5983

    CAS  PubMed  Google Scholar 

  31. Miyoshi K, Shillingford JM, Smith GH, Grimm SL, Wagner KU, Oka T, Rosen JM, Robinson GW, Hennighausen L (2001) Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol 155:531–542

    CAS  PubMed  Google Scholar 

  32. Moz Y, Silver J, Naveh-Many T (2003) Characterization of cis-acting element in renal NaPi-2 cotransporter mRNA that determines mRNA stability. Am J Physiol 284:F663–F670

    CAS  Google Scholar 

  33. Murer H, Hernando N, Forster I, Biber J (2000) Proximal tubular phosphate reabsorption. Physiol Rev 80:1373–1409

    CAS  PubMed  Google Scholar 

  34. Pfister MF, Ruf I, Stange G, Ziegler U, Lederer E, Biber J, Murer H (1998) Parathyroid hormone leads to the lysosomal degradation of the renal type II Na+/Pi-cotransporter . Proc Natl Acad Sci USA 95:1909–1914

    CAS  PubMed  Google Scholar 

  35. Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B, Hulin P, Benoue-Blanchet F, Silve C, Grandchamp B, Friedlander G (2002) Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 347:983–991

    Google Scholar 

  36. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto KI (2002) Growth-related renal type ll Na/Pi cotransporter. J Biol Chem 277:19665–19672

    Article  CAS  PubMed  Google Scholar 

  37. Shenolikar S, Voltz JW, Minkoff CM, Wade JB, Weinman EJ (2202) 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 USA 99:11470–11475

    Article  Google Scholar 

  38. Silve C, Friedlander G (2000) Renal regulation of phosphate excretion. In: Seldin DW, Giebisch G (eds) The kidney, physiology and pathophysiology. Lippincott Williams & Williams, pp 1885–1904

  39. Tatsumi S, Miyamoto KI, Kouda T, Motonaga K, Katai K, Ohkido I, Morita K, Segawa H, Tani Y, Yamamoto H, Taketani Y, Takeda E (1998) Identification of three isoforms for the Na-dependent phosphate cotransporter (NaPi-2) in rat kidney. J Biol Chem 273:28568–28575

    CAS  PubMed  Google Scholar 

  40. Tennenhouse HS, Sabbagh Y (2002) Novel phosphate-regulating genes in the pathogenesis of renal phosphate wasting disorders. Pflugers Arch 444:317–326

    PubMed  Google Scholar 

  41. Traebert M, Hattenhauer O, Murer H, Kaissling B, Biber J (1999) Expression of a type II sodium-phosphate cotransporter in murine type II alveolar epithelial cells. Am J Physiol 277:L868–L873

    CAS  PubMed  Google Scholar 

  42. Werner A, Kinne RKH (2001) Evolution of the Na-Pi cotransport systems. Am J Physiol 280:R301–R312

    PubMed  Google Scholar 

  43. Xu H, Collins JF, Bai L, Kiela PR, Ghishan FK (2001) Regulation of the human sodium-phosphate cotransporter NaPi-llb gene promoter by epidermal growth factor. Am J Physiol 280:C628–C636

    CAS  Google Scholar 

  44. Xu H, Bai L, Collins JF, Ghishan FK (2002) Age-dependent regulation of rat intestinal type llb sodiumm-phosphate cotransporter by 1,25-(OH)2 vitamin D3. Am J Physiol 282:C487–C493

    CAS  Google Scholar 

Download references

Acknowledgements

We thank the Swiss Science National Foundations and other Swiss financial institutions for their financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heini Murer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murer, H., Forster, I. & Biber, J. The sodium phosphate cotransporter family SLC34. Pflugers Arch - Eur J Physiol 447, 763–767 (2004). https://doi.org/10.1007/s00424-003-1072-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1072-5

Keywords

Navigation