Pendrin

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Pendrin
Identifiers
AliasesIPR030285
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Pendrin is an anion exchange protein that in humans is encoded by the SLC26A4 gene (solute carrier family 26, member 4).[1][2] Pendrin was initially identified as a sodium-independent chloride-iodide exchanger[3] with subsequent studies showing that it also accepts formate and bicarbonate as substrates.[4][5] Pendrin is similar to the Band 3 transport protein found in red blood cells. Pendrin is the protein which is mutated in Pendred syndrome, which is an autosomal recessive disorder characterized by sensorineural hearing loss, goiter and a partial organification problem detectable by a positive perchlorate test.[6]

Pendrin is responsible for mediating the electroneutral exchange of chloride (Cl) for bicarbonate (HCO3) across a plasma membrane in the chloride cells of freshwater fish.

By phylogenetic analysis, pendrin has been found to be a close relative of prestin present on the hair cells or organ of corti in the inner ear. Prestin is primarily an electromechanical transducer but pendrin is an ion transporter.

Function[edit]

Pendrin is an ion exchanger found in many types of cells in the body. High levels of pendrin expression have been identified in the inner ear and thyroid. In the thyroid, pendrin mediates a component of the efflux of iodide across the apical membrane of the thyrocyte, which is critical for the formation of thyroid hormone.[7] The exact function of pendrin in the inner ear remains unclear; however, pendrin may play a role in acid-base balance as a chloride-bicarbonate exchanger, regulate volume homeostasis through its ability to function as a chloride-formate exchanger[8][9] or indirectly modulate the calcium concentration of the endolymph.[10] Pendrin is also expressed in the kidney, and has been localized to the apical membrane of a population of intercalated cells in the cortical collecting duct where it is involved in bicarbonate secretion.[11][12]

Thyroid hormone synthesis, with Pendrin seen at center between the follicular colloid and the follicular cell.

Clinical significance[edit]

Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. Pendred syndrome is characterized by thyroid goiter and enlargement of the vestibular aqueduct resulting in deafness; however, despite being expressed in the kidney, individuals with Pendred syndrome do not show any kidney-related acid-base, or volume abnormalities under basal conditions. This is probably the result of other bicarbonate or chloride transporters in the kidney compensating for any loss of pendrin function. Only under extreme situations of salt depletion or metabolic alkalosis, or with inactivation of the sodium-chloride cotransporter, are fluid and electrolyte disorders manifested in these patients.[13] SLC26A4 is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters.[1]

Another little-understood role of pendrin is in airway hyperreactivity and inflammation, as during asthma attacks and allergic reactions. Expression of pendrin in the lung increases in response to allergens and high concentrations of IL-13,[14][15] and overexpression of pendrin results in airway inflammation, hyperreactivity, and increased mucus production.[16][17] These symptoms could result from pendrin's effects on ion concentration in the airway surface liquid, possibly causing the liquid to be less hydrated.[18]

References[edit]

  1. ^ a b "Entrez Gene: SLC26A4 solute carrier family 26, member 4".
  2. ^ Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED (December 1997). "Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)". Nature Genetics. 17 (4): 411–22. doi:10.1038/ng1297-411. PMID 9398842. S2CID 39359838.
  3. ^ Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP (April 1999). "The Pendred syndrome gene encodes a chloride-iodide transport protein". Nature Genetics. 21 (4): 440–3. doi:10.1038/7783. PMID 10192399. S2CID 23717390.
  4. ^ Scott DA, Karniski LP (January 2000). "Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange". American Journal of Physiology. Cell Physiology. 278 (1): C207-11. doi:10.1152/ajpcell.2000.278.1.c207. PMID 10644529.
  5. ^ Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, Burnham CE (February 2001). "Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex". American Journal of Physiology. Renal Physiology. 280 (2): F356-64. doi:10.1152/ajprenal.2001.280.2.f356. PMID 11208611.
  6. ^ Patterson C, Runge MS (2006). Principles of molecular medicine. Totowa, NJ: Humana Press. p. 957. ISBN 1-58829-202-9.
  7. ^ Bizhanova A, Kopp P (2011-01-01). "Controversies concerning the role of pendrin as an apical iodide transporter in thyroid follicular cells". Cellular Physiology and Biochemistry. 28 (3): 485–90. doi:10.1159/000335103. PMID 22116361.
  8. ^ Karniski LP, Aronson PS (September 1985). "Chloride/formate exchange with formic acid recycling: a mechanism of active chloride transport across epithelial membranes". Proceedings of the National Academy of Sciences of the United States of America. 82 (18): 6362–5. Bibcode:1985PNAS...82.6362K. doi:10.1073/pnas.82.18.6362. PMC 391054. PMID 3862136.
  9. ^ Kim HM, Wangemann P (November 2010). "Failure of fluid absorption in the endolymphatic sac initiates cochlear enlargement that leads to deafness in mice lacking pendrin expression". PLOS ONE. 5 (11): e14041. Bibcode:2010PLoSO...514041K. doi:10.1371/journal.pone.0014041. PMC 2984494. PMID 21103348.
  10. ^ Wangemann P, Nakaya K, Wu T, Maganti RJ, Itza EM, Sanneman JD, Harbidge DG, Billings S, Marcus DC (May 2007). "Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model". American Journal of Physiology. Renal Physiology. 292 (5): F1345-53. doi:10.1152/ajprenal.00487.2006. PMC 2020516. PMID 17299139.
  11. ^ Wall SM (2006). "The renal physiology of pendrin (SLC26A4) and its role in hypertension". Novartis Foundation Symposium. Novartis Foundation Symposia. 273: 231–9, discussion 239–43, 261–4. doi:10.1002/0470029579.ch15. ISBN 978-0-470-02957-2. PMID 17120771.
  12. ^ Royaux IE, Wall SM, Karniski LP, Everett LA, Suzuki K, Knepper MA, Green ED (March 2001). "Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion". Proceedings of the National Academy of Sciences of the United States of America. 98 (7): 4221–6. Bibcode:2001PNAS...98.4221R. doi:10.1073/pnas.071516798. PMC 31206. PMID 11274445.
  13. ^ Pela I, Bigozzi M, Bianchi B (June 2008). "Profound hypokalemia and hypochloremic metabolic alkalosis during thiazide therapy in a child with Pendred syndrome". Clinical Nephrology. 69 (6): 450–3. doi:10.5414/cnp69450. PMID 18538122.
  14. ^ Kuperman DA, Lewis CC, Woodruff PG, Rodriguez MW, Yang YH, Dolganov GM, Fahy JV, Erle DJ (August 2005). "Dissecting asthma using focused transgenic modeling and functional genomics". The Journal of Allergy and Clinical Immunology. 116 (2): 305–11. doi:10.1016/j.jaci.2005.03.024. PMID 16083784.
  15. ^ Zhen G, Park SW, Nguyenvu LT, Rodriguez MW, Barbeau R, Paquet AC, Erle DJ (February 2007). "IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production". American Journal of Respiratory Cell and Molecular Biology. 36 (2): 244–53. doi:10.1165/rcmb.2006-0180OC. PMC 1899314. PMID 16980555.
  16. ^ Pedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, Di Candia M, Bandettini R, Ravazzolo R, Zegarra-Moran O, Galietta LJ (April 2007). "Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: role of pendrin and anion channels". Journal of Immunology. 178 (8): 5144–53. doi:10.4049/jimmunol.178.8.5144. PMID 17404297.
  17. ^ Nakao I, Kanaji S, Ohta S, Matsushita H, Arima K, Yuyama N, Yamaya M, Nakayama K, Kubo H, Watanabe M, Sagara H, Sugiyama K, Tanaka H, Toda S, Hayashi H, Inoue H, Hoshino T, Shiraki A, Inoue M, Suzuki K, Aizawa H, Okinami S, Nagai H, Hasegawa M, Fukuda T, Green ED, Izuhara K (May 2008). "Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease". Journal of Immunology. 180 (9): 6262–9. doi:10.4049/jimmunol.180.9.6262. PMID 18424749.
  18. ^ Nakagami Y, Favoreto S, Zhen G, Park SW, Nguyenvu LT, Kuperman DA, Dolganov GM, Huang X, Boushey HA, Avila PC, Erle DJ (August 2008). "The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model". Journal of Immunology. 181 (3): 2203–10. doi:10.4049/jimmunol.181.3.2203. PMC 2491716. PMID 18641360.

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