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Sodium/phosphate cotransporter

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Template:PBB The Sodium/Phosphate Cotransporter (also known as the Na+-Pi Cotransport Protein (NaPi-2a), Sodium-dependent Phosphate Transporter or Phosphate:Na+ Symporter) is a member of the Phosphate:Na+ Symporter (PNaS) Family under the TOG Superfamily of transport proteins as defined by the Transporter Classification Database.

The PNaS Family of Transport Proteins

The Phosphate:Na+ Symporter (PNaS) family (TC# 2.A.58) includes several closely related, functionally characterized, sodium-dependent, inorganic phosphate (Pi) transporter (NPT2) proteins from mammals. Other organisms that possess NPT2 homologues are fish and the worm, C. elegans, although these homologues are functionally uncategorized. One closely related bacterial protein, NptA of Vibrio cholerae, resembles the animal proteins to a much greater degree (34% identity; 51% similarity to many mammalian Npt2 symporters [1]) than to any other bacterial homologue. This may be evidence that the gene was obtained through lateral transfer from a eukaryotic source. The well-characterized mammalian proteins are found in renal (IIa isoform) and intestinal (IIb isoform) brush border membranes and are about 640 amino acyl residues long with 8-12 putative TMSs. The N- and C-termini both reside in the cytoplasm, and a large hydrophilic loop is localized between trans-membrane segments (TMSs) 3 and 4. While IIa isoforms are pH-dependent, IIb isoforms are found to be pH-independent.[2] The IIa SodiumPphosphate Symporter isoform is a functional monomer,[3] but it interacts with PDZ proteins which probably mediate apical sorting, parathyroid hormone-controlled endocytosis and/or lysosomal sorting of internalized transporter.[1][4]

Reaction

The transport reaction catalyzed by the mammalian proteins is:[1]

Pi (out) + 3 Na+ (out) ⇌ Pi (in) + 3 Na+ (in).

PNaS Proteins in Mammals

There are several known sodium-dependent phosphate transporters found in humans. For example, solute carrier family 34, member 1 (SLC34A1) a protein in humans that is encoded by the SLC34A1 gene [5] and fascilitates uptake of phosphate for normal cellular functions including cellular metabolism, signal transduction, and nucleic acid and lipid synthesis.

Other known sodium-dependent phosphate transporters found in humans include (but are not limited to):

Function

The IIa syporter isoform is can be found in a range of tissues, but most noteably in the proximal tubule of the nephron. In this case, it is responsible for reabsorbing approximately 80% of the phosphate that has been filtered out at the glomerulus. The transporter moves hydrogen phosphate (HPO42−) into the cell along with 3 sodium ions (Na+). Alternatively, it can also move dihydrogen phosphate (H2PO4−) along with 2 Na+. For both movements the net charge is +1. Once inside the cell, hydrogen phosphate and dihydrogen phosphate may react with water to form each other. Transport of these chemicals out of the cell at the basolateral surface is not currently understood.[1][6] The type IIa cotransporter is regulated by parathyroid hormone (PTH). PTH acts to decrease phosphate reabsorption from the renal filtrate and therefore promote its excretion into the urine. It does this by causing for endocytosis of NaPi transporters on the apical surface of the cell. With less transporters available, more phosphate is lost in the urine.[6]

Clinical significance

Mutations in this gene are associated with hypophosphatemia nephrolithiasis/osteoporosis 1.[5]

See also

References

  1. ^ a b c d Saier, Milton. "Transporter Classification Database: 2.A.58 The Phosphate:Na+ Symporter (PNaS) Family". tcdb.org.
  2. ^ de la Horra, C; Hernando, N; Lambert, G; Forster, I; Biber, J; Murer, H (March 3, 2000). "Molecular determinants of pH sensitivity of the type IIa Na/P(i) cotransporter". J Biol Chem. 275 (9): 6284–7. PMID 10692425.
  3. ^ Köhler, K; Forster, IC; Lambert, G; Biber, J; Murer, H (August 25, 2000). "The functional unit of the renal type IIa Na+/Pi cotransporter is a monomer". J Biol Chem. 275 (34): 26113–20. PMID 10859311.
  4. ^ Gisler, SM; Stagljar, I; Traebert, M; Bacic, D; Biber, J; Murer, H (March 23, 2000). "Interaction of the type IIa Na/Pi cotransporter with PDZ proteins". J Biol Chem. 276 (12): 9206–13. PMID 11099500.
  5. ^ a b "Entrez Gene: Solute carrier family 34 (sodium phosphate), member 1".
  6. ^ a b Boron WF, Boulpaep EL (2012). Medical Physiology: a cellular and molecular approach (2 ed.). Philadelphia: Saunders. ISBN 1-4377-1753-5.

Further reading

  • Tenenhouse H (1999). "X-linked hypophosphataemia: a homologous disorder in humans and mice". Nephrol Dial Transplant. 14 (2): 333–41. doi:10.1093/ndt/14.2.333. PMID 10069185.
  • Murer, H; Hernando, N; Forster, I; Biber, J (October 2000). "Proximal tubular phosphate reabsorption: molecular mechanisms". Physiol Rev. 80 (4): 1373–409. PMID 11015617.
  • Fenollar-Ferrer, C; Forster, IC; Patti, M; Knoepfel, T; Werner, A; Forrest, LR (May 19, 2015). "Identification of the first sodium binding site of the phosphate cotransporter NaPi-IIa (SLC34A1)". Biophys J. 108 (10): 2465–80. doi:10.1016/j.bpj.2015.03.054. PMID 25992725.


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