Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi


Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101880-1


Historical Background

All living beings need inorganic phosphate for many essential functions, including metabolism (high-energy bonds, signal transduction, pH control, etc.) and molecular components (membrane phospholipids, nucleotides, minerals, etc.). Because Pi is a polyprotic acid, it is ionized at life-compatible pHs with one or two negative charges, a characteristic that impairs the free entrance to the cell through lipid membranes. Therefore, all cells and living beings need Pi transporters in their plasma membranes, requiring energy to overcome the transmembrane potential (negative inside). The universal need of Piexplains the presence of the solute carrier family 20 (Slc20) of phosphate in all organisms, from bacteria and plants to fungi and animals, using either proton or sodium gradients as driving forces. A detailed evolutionary description of the Slc20 family can be found elsewhere...


Slc20 Family Ectopic Calcification Slc20 Transporter Primary Familial Brain Calcification Idiopathic Basal Ganglion Calcification 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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  1. Beck L, Leroy C, Salaün C, Margall-Ducos G, Desdouets C, Friedlander G. Identification of a novel function of PiT1 critical for cell proliferation and independent of its phosphate transport activity. J Biol Chem. 2009;284:31363–74. doi:10.1074/jbc.M109.053132.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bøttger P, Pedersen L. Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life. BMC Biochem. 2011;12:21. doi:10.1186/1471-2091-12-21.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bourgine A, Pilet P, Diouani S, Sourice S, Lesoeur J, Beck-Cormier S, Khoshniat S, Weiss P, Friedlander G, Guicheux J, Beck L. Mice with hypomorphic expression of the sodium-phosphate cotransporter PiT1/Slc20a1 have an unexpected normal bone mineralization. PLoS One. 2013;8:e65979. doi:10.1371/journal.pone.0065979.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Farrell KB, Tusnady GE, Eiden MV. New structural arrangement of the extracellular regions of the phosphate transporter SLC20A1, the receptor for gibbon ape leukemia virus. J Biol Chem. 2009;284:29979–87. doi:10.1074/jbc.M109.022566.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Forster I, Hernando N, Sorribas V, Werner A. Phosphate transporters in renal, gastrointestinal, and other tissues. Adv Chronic Kidney Dis. 2011;18:63–76. doi:10.1053/j.ackd.2011.01.006.CrossRefPubMedGoogle Scholar
  6. Forster IC, Hernando N, Biber J, Murer H. Phosphate transporters of the SLC20 and SLC34 families. Mol Asp Med. 2013;34:386–95. doi:10.1016/j.mam.2012.07.007.CrossRefGoogle Scholar
  7. Giral H, Caldas Y, Sutherland E, Wilson P, Breusegem S, Barry N, Blaine J, Jiang T, Wang XX, Levi M. Regulation of rat intestinal Na-dependent phosphate transporters by dietary phosphate. Am J Physiol Renal Physiol. 2009;297:F1466–75.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Hortells L, Sosa C, Millán Á, Sorribas V. Critical parameters of the in vitro method of vascular smooth muscle cell calcification. PLoS One. 2015;10:e0141751. doi:10.1371/journal.pone.0141751.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kavanaugh MP, Miller DG, Zhang W, Law W, Kozak SL, Kabat D, Miller AD. Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. Proc Natl Acad Sci U S A. 1994;91:7071–5.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Larsen FT, Jensen N, Autzen JK, Kongsfelt IB, Pedersen L. Primary brain calcification causal pit2 transport-knockout variants can exert dominant negative effects on wild-type pit2 transport function in mammalian cells. J Mol Neurosci. 2016. doi:10.1007/s12031-016-0868-7.PubMedCentralGoogle Scholar
  11. Mizobuchi M, Ogata H, Hatamura I, Koiwa F, Saji F, Shiizaki K, Negi S, Kinugasa E, Ooshima A, Koshikawa S, Akizawa T. Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism. Nephrol Dial Transplant. 2006;21:911–6. doi:10.1093/ndt/gfk008.CrossRefPubMedGoogle Scholar
  12. Olah Z, Lehel C, Anderson WB, Eiden MV, Wilson CA. The cellular receptor for gibbon ape leukemia virus is a novel high affinity sodium-dependent phosphate transporter. J Biol Chem. 1994;269:25426–31.PubMedGoogle Scholar
  13. Palmer G, Zhao J, Bonjour J, Hofstetter W, Caverzasio J. In vivo expression of transcripts encoding the Glvr-1 phosphate transporter/retrovirus receptor during bone development. Bone. 1999;24:1–7. doi:10.1016/S8756-3282(98)00151-3.CrossRefPubMedGoogle Scholar
  14. Picard N, Capuano P, Stange G, Mihailova M, Kaissling B, Murer H, Biber J, Wagner CA. Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters. Pflugers Arch. 2010;460:677–87. doi:10.1007/s00424-010-0841-1.CrossRefPubMedGoogle Scholar
  15. Ravera S, Virkki LV, Murer H, Forster IC. Deciphering PiT transport kinetics and substrate specificity using electrophysiology and flux measurements. Am J Physiol Cell Physiol. 2007;293:C606–20. doi:10.1152/ajpcell.00064.2007.CrossRefPubMedGoogle Scholar
  16. Ravera S, Murer H, Forster IC. An externally accessible linker region in the sodium-coupled phosphate transporter PiT-1 (SLC20A1) is important for transport function. Cell Physiol Biochem. 2013;32:187–99. doi:10.1159/000350135.CrossRefPubMedGoogle Scholar
  17. Rodrigues P, Heard JM. Modulation of phosphate uptake and amphotropic murine leukemia virus entry by posttranslational modifications of PIT-2. J Virol. 1999;73:3789–99.PubMedPubMedCentralGoogle Scholar
  18. Salaün C, Rodrigues P, Heard JM. Transmembrane topology of PiT-2, a phosphate transporter-retrovirus receptor. J Virol. 2001;75:5584–92. doi:10.1128/JVI.75.12.5584-5592.2001.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Salaün C, Gyan E, Rodrigues P, Heard JM. Pit2 assemblies at the cell surface are modulated by extracellular inorganic phosphate concentration. J Virol. 2002;76:4304–11. doi:10.1128/JVI.76.9.4304-4311.2002.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Salaün C, Leroy C, Rousseau A, Boitez V, Beck L, Friedlander G. Identification of a novel transport-independent function of PiT1/SLC20A1 in the regulation of TNF-induced apoptosis. J Biol Chem. 2010;285:34408–18. doi:10.1074/jbc.M110.130989.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Suzuki A, Ghayor C, Guicheux J, Magne D, Quillard S, Kakita A, Ono Y, Miura Y, Oiso Y, Itoh M, Caverzasio J. Enhanced expression of the inorganic phosphate transporter Pit-1 is involved in BMP-2-induced matrix mineralization in osteoblast-like cells. J Bone Miner Res. 2006;21:674–83. doi:10.1359/jbmr.020603.CrossRefPubMedGoogle Scholar
  22. Tatsumi S, Segawa H, Morita K, Haga H, Kouda T, Yamamoto H, Inoue Y, Nii T, Katai K, Taketani Y, Miyamoto KI, Takeda E. Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands. Endocrinology. 1998;139:1692–9. doi:10.1210/endo.139.4.5925.CrossRefPubMedGoogle Scholar
  23. Villa-Bellosta R, Bogaert YE, Levi M, Sorribas V. Characterization of phosphate transport in rat vascular smooth muscle cells: implications for vascular calcification. Arterioscler Thromb Vasc Biol. 2007;27:1030–6. doi:10.1161/ATVBAHA.106.132266.CrossRefPubMedGoogle Scholar
  24. Villa-Bellosta R, Sorribas V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler Thromb Vasc Biol. 2009;29:761–6. doi:10.1161/ATVBAHA.108.183384.CrossRefPubMedGoogle Scholar
  25. Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H, Biber J, Forster IC. 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. 2009a;296:F691–9. doi:10.1152/ajprenal.90623.2008.CrossRefPubMedGoogle Scholar
  26. Villa-Bellosta R, Levi M, Sorribas V. Vascular smooth muscle cell calcification and SLC20 inorganic phosphate transporters: effects of PDGF, TNF-alpha, and Pi. Pflugers Arch. 2009b;458:1151–61. doi:10.1007/s00424-009-0688-5.CrossRefPubMedGoogle Scholar
  27. Wang C, Li Y, Shi L, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintáns B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X, Liu JY. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012;44:254–6. doi:10.1038/ng.1077.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Laboratory of Molecular ToxicologyUniversity of ZaragozaZaragozaSpain