The Na+-Picotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi

American Journal of Physiology - Renal Physiology - Tập 296 Số 4 - Trang F691-F699 - 2009
Ricardo Villa‐Bellosta1, Silvia Ravera, Vı́ctor Sorribas, Gerti Stange, Moshe Levi, Heini Murer, Jürg Biber, Ian C. Forster
1Institute of Physiology, Univ. of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Tóm tắt

The principal mediators of renal phosphate (Pi) reabsorption are the SLC34 family proteins NaPi-IIa and NaPi-IIc, localized to the proximal tubule (PT) apical membrane. Their abundance is regulated by circulatory factors and dietary Pi. Although their physiological importance has been confirmed in knockout animal studies, significant Pireabsorptive capacity remains, which suggests the involvement of other secondary-active Pitransporters along the nephron. Here we show that a member of the SLC20 gene family (PiT-2) is localized to the brush-border membrane (BBM) of the PT epithelia and that its abundance, confirmed by Western blot and immunohistochemistry of rat kidney slices, is regulated by dietary Pi. In rats treated chronically on a high-Pi(1.2%) diet, there was a marked decrease in the apparent abundance of PiT-2 protein in kidney slices compared with those from rats kept on a chronic low-Pi(0.1%) diet. In Western blots of BBM from rats that were switched from a chronic low- to high-Pidiet, NaPi-IIa showed rapid downregulation after 2 h; PiT-2 was also significantly downregulated at 24 h and NaPi-IIc after 48 h. For the converse dietary regime, NaPi-IIa showed adaptation within 8 h, whereas PiT-2 and NaPi-IIc showed a slower adaptive trend. Our findings suggest that PiT-2, until now considered as a ubiquitously expressed Pihousekeeping transporter, is a novel mediator of Pireabsorption in the PT under conditions of acute Pideprivation, but with a different adaptive time course from NaPi-IIa and NaPi-IIc.

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Tài liệu tham khảo

10.1073/pnas.0505882102

10.1152/ajpcell.2000.279.4.C1135

10.1073/pnas.95.9.5372

10.1146/annurev.physiol.69.040705.141729

Berndt TJ, Kumar R.Clinical disturbances of phosphate homeostasis. In:Seldin and Giebisch's The Kidney, edited by Alpern RJ and Hebert SC. New York, NY: Academic, 2008, p. 1989–2006.

10.1038/nprot.2007.156

10.1007/s002329900394

Chien ML, Foster JL, Douglas JL, Garcia JV.The amphotropic murine leukemia virus receptor gene encodes a 71-kilodalton protein that is induced by phosphate depletion.J Virol71: 4564–4570, 1997.

10.1152/ajprenal.1994.266.5.F767

10.1074/mcp.M500078-MCP200

10.1152/ajpheart.1999.277.2.H543

10.1038/sj.ki.5001813

10.1152/ajprenal.1999.276.4.F644

10.1152/ajpgi.00272.2004

10.1161/01.RES.0000161997.24797.c0

Gottschalk CW, Lassiter WE, Mylle M.Localization of urine acidification in the mammalian kidney.Am J Physiol198: 581–585, 1960.

10.1038/ki.1996.135

10.1073/pnas.91.15.7071

10.1152/ajprenal.00075.2006

10.1055/s-2005-870096

10.1152/ajprenal.1994.267.5.F900

10.1097/MNH.0b013e3281c55ef1

10.1161/01.RES.0000216409.20863.e7

10.1172/JCI119289

Madjdpour C, Bacic D, Kaissling B, Murer H, Biber J.Segment-specific expression of sodium-phosphate cotransporters NaPi-IIa and -IIc and interacting proteins in mouse renal proximal tubules.Pflugers Arch448: 402–410, 2004.

10.1159/000107069

Murer H, Forster I, Hilfiker H, Pfister M, Kaissling B, Lotscher M, Biber J.Cellular/molecular control of renal Na/Pi-cotransport.Kidney Int Suppl65: S2–S10, 1998.

Murer H, Forster IC, Hernando N, Biber J.Proximal Tubular Handling of Phosphate: Na/Pi-Cotransporters and their Regulation. In:Seldin and Giebisch's The Kidney, edited by Alpern RJ and Hebert SC. New York, NY: Acdemic, 2008, p. 1979–1988.

10.1152/physrev.2000.80.4.1373

10.1152/ajpcell.1991.260.5.C885

10.2133/dmpk.23.22

10.1007/s00424-008-0530-5

10.1007/s00424-003-1010-6

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 Chem269: 25426–25431, 1994.

10.1007/s004240050573

10.1152/ajpcell.00064.2007

10.1046/j.1523-1755.1999.055003976.x

10.1128/JVI.75.12.5584-5592.2001

Saliba KJ, Martin RE, Broer A, Henry RI, McCarthy CS, Downie MJ, Allen RJ, Mullin KA, McFadden GI, Broer S, Kirk K.Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite.Nature443: 582–585, 2006.

10.1074/jbc.M200943200

Segawa H, Onitsuka A, Aranami F, Tomeo Y, Kaneko I, Furutani J, Ito M, Matsumoto M, Li M, Amizuka N, Kuwahata M, Miyamoto KI.Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development.J Amer Soc NephrolSA-FC101, 2007.

10.1152/ajprenal.00097.2004

Segel IH.Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-state Enzyme Systems.New York, NY: Wiley, 1975.

Szczepanska-Konkel M, Yusufi AN, VanScoy M, Webster SK, Dousa TP.Phosphonocarboxylic acids as specific inhibitors of Na+-dependent transport of phosphate across renal brush border membrane.J Biol Chem261: 6375–6383, 1986.

10.1210/endo.139.4.5925

10.1152/ajprenal.00252.2003

10.1152/ajpheart.1998.275.2.H527

Traebert M, Lotscher M, Aschwanden R, Ritthaler T, Biber J, Murer H, Kaissling B.Distribution of the sodium/phosphate transporter during postnatal ontogeny of the rat kidney.J Am Soc Nephrol10: 1407–1415, 1999.

Vieira FL, Malnic G.Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode.Am J Physiol214: 710–718, 1968.

10.1038/sj.ki.5002703

10.1161/ATVBAHA.106.132266

10.1016/j.taap.2008.05.026

10.1152/ajprenal.00228.2007

10.1152/ajprenal.00293.2004

10.1128/MCB.00104-07

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American Journal of Physiology - Renal Physiology

Tập 296 Số 4

F691-F699

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