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.
Similar content being viewed by others
References
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
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
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
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
Cross HS, Debiec H, Peterlik M (1990) Mechanism and regulation of intestinal phosphate absorption. Miner Electrolyte Metab 16:115–124
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
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
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
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
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
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
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
Gupta A, Guo XL, Alvarez UM, Hruska KA (1997) Regulation of sodium-dependent phosphate transport in osteoclasts. J Clin Invest 100:538–548
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
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
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
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
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
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
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
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
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
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
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
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
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
Levi M, Kempson SA, Lötscher M, Biber J, Murer H (1996) Molecular regulation of renal phosphate transport. J Membr Biol 154:1–9
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
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
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
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
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
Murer H, Hernando N, Forster I, Biber J (2000) Proximal tubular phosphate reabsorption. Physiol Rev 80:1373–1409
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
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
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
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
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
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
Tennenhouse HS, Sabbagh Y (2002) Novel phosphate-regulating genes in the pathogenesis of renal phosphate wasting disorders. Pflugers Arch 444:317–326
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
Werner A, Kinne RKH (2001) Evolution of the Na-Pi cotransport systems. Am J Physiol 280:R301–R312
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
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
Acknowledgements
We thank the Swiss Science National Foundations and other Swiss financial institutions for their financial support.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-003-1072-5