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...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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. https://doi.org/10.1074/jbc.M109.053132.
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. https://doi.org/10.1186/1471-2091-12-21.
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. https://doi.org/10.1371/journal.pone.0065979.
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. https://doi.org/10.1074/jbc.M109.022566.
Forster I, Hernando N, Sorribas V, Werner A. Phosphate transporters in renal, gastrointestinal, and other tissues. Adv Chronic Kidney Dis. 2011;18:63–76. https://doi.org/10.1053/j.ackd.2011.01.006.
Forster IC, Hernando N, Biber J, Murer H. Phosphate transporters of the SLC20 and SLC34 families. Mol Asp Med. 2013;34:386–95. https://doi.org/10.1016/j.mam.2012.07.007.
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.
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. https://doi.org/10.1371/journal.pone.0141751.
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.
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. https://doi.org/10.1007/s12031-016-0868-7.
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. https://doi.org/10.1093/ndt/gfk008.
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.
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. https://doi.org/10.1016/S8756-3282(98)00151-3.
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. https://doi.org/10.1007/s00424-010-0841-1.
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. https://doi.org/10.1152/ajpcell.00064.2007.
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. https://doi.org/10.1159/000350135.
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.
Salaün C, Rodrigues P, Heard JM. Transmembrane topology of PiT-2, a phosphate transporter-retrovirus receptor. J Virol. 2001;75:5584–92. https://doi.org/10.1128/JVI.75.12.5584-5592.2001.
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. https://doi.org/10.1128/JVI.76.9.4304-4311.2002.
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. https://doi.org/10.1074/jbc.M110.130989.
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. https://doi.org/10.1359/jbmr.020603.
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. https://doi.org/10.1210/endo.139.4.5925.
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. https://doi.org/10.1161/ATVBAHA.106.132266.
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. https://doi.org/10.1161/ATVBAHA.108.183384.
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. https://doi.org/10.1152/ajprenal.90623.2008.
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. https://doi.org/10.1007/s00424-009-0688-5.
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. https://doi.org/10.1038/ng.1077.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Sorribas, V. (2018). SLC20. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101880
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101880
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences