Pendrin

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.{{cite journal | vauthors = Bizhanova A, Kopp P | title = Controversies concerning the role of pendrin as an apical iodide transporter in thyroid follicular cells | journal = Cellular Physiology and Biochemistry | volume = 28 | issue = 3 | pages = 485–490 | date = 2011-01-01 | pmid = 22116361 | doi = 10.1159/000335103 | doi-access = free }}

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

In the thyroid, pendrin is expressed by thyroid follicular cells. Na⁺/I⁻ symporter imports iodide (I⁻) into the cell across its basolateral side, and pendrin extrudes the I⁻ across the cell's apical membrane into the thyroid colloid.{{cite journal | vauthors = Kessler J, Obinger C, Eales G | title = Factors influencing the study of peroxidase-generated iodine species and implications for thyroglobulin synthesis | journal = Thyroid | volume = 18 | issue = 7 | pages = 769–774 | date = July 2008 | pmid = 18631006 | doi = 10.1089/thy.2007.0310 }}

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{{cite journal | vauthors = Karniski LP, Aronson PS | title = Chloride/formate exchange with formic acid recycling: a mechanism of active chloride transport across epithelial membranes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 18 | pages = 6362–6365 | date = September 1985 | pmid = 3862136 | pmc = 391054 | doi = 10.1073/pnas.82.18.6362 | doi-access = free | bibcode = 1985PNAS...82.6362K }}{{cite journal | vauthors = Kim HM, Wangemann P | title = Failure of fluid absorption in the endolymphatic sac initiates cochlear enlargement that leads to deafness in mice lacking pendrin expression | journal = PLOS ONE | volume = 5 | issue = 11 | pages = e14041 | date = November 2010 | pmid = 21103348 | pmc = 2984494 | doi = 10.1371/journal.pone.0014041 | doi-access = free | bibcode = 2010PLoSO...514041K }} or indirectly modulate the calcium concentration of the endolymph.{{cite journal | vauthors = Wangemann P, Nakaya K, Wu T, Maganti RJ, Itza EM, Sanneman JD, Harbidge DG, Billings S, Marcus DC | title = Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model | journal = American Journal of Physiology. Renal Physiology | volume = 292 | issue = 5 | pages = F1345–F1353 | date = May 2007 | pmid = 17299139 | pmc = 2020516 | doi = 10.1152/ajprenal.00487.2006 }} 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.{{cite book | vauthors = Wall SM | chapter = The Renal Physiology of Pendrin (SLC26A4) and Its Role in Hypertension | title = Epithelial Anion Transport in Health and Disease: The Role of the SLC26 Transporters Family | volume = 273 | pages = 231–9; discussion 239–43, 261–4 | year = 2006 | pmid = 17120771 | doi = 10.1002/0470029579.ch15 | isbn = 978-0-470-02957-2 | series = Novartis Foundation Symposia }}{{cite journal | vauthors = Royaux IE, Wall SM, Karniski LP, Everett LA, Suzuki K, Knepper MA, Green ED | title = Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 7 | pages = 4221–4226 | date = March 2001 | pmid = 11274445 | pmc = 31206 | doi = 10.1073/pnas.071516798 | doi-access = free | bibcode = 2001PNAS...98.4221R }}

Renal β-intercalated cells of the late distal tube and collecting duct express pendrin upon their apical membrane, resorbing one Cl⁻ in exchange for secreting a HCO3⁻, with Cl⁻ subsequently extruded from the cell by a basolateral Cl⁻ channel. β-intercalated cells thus utilise pendrin to contribute to acid-base homeostasis by excreting base (HCO3⁻) into urine. Additionally, β-intercalated cells may use pendrin in concert with a Na⁺/HCO3⁻/2Cl⁻ antiporter in order to resorb NaCl.{{Cite book |title=Berne & Levy Physiology |publisher=Elsevier |year=2024 |isbn=978-0-323-84790-2 | veditors = Koeppen BM, Stanton BA, Swiatecka-Urban A |edition=8th |location=Philadelphia, PA }}

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.{{cite journal | vauthors = Pela I, Bigozzi M, Bianchi B | title = Profound hypokalemia and hypochloremic metabolic alkalosis during thiazide therapy in a child with Pendred syndrome | journal = Clinical Nephrology | volume = 69 | issue = 6 | pages = 450–453 | date = June 2008 | pmid = 18538122 | doi = 10.5414/cnp69450 }} 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.

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,{{cite journal | vauthors = Kuperman DA, Lewis CC, Woodruff PG, Rodriguez MW, Yang YH, Dolganov GM, Fahy JV, Erle DJ | title = Dissecting asthma using focused transgenic modeling and functional genomics | journal = The Journal of Allergy and Clinical Immunology | volume = 116 | issue = 2 | pages = 305–311 | date = August 2005 | pmid = 16083784 | doi = 10.1016/j.jaci.2005.03.024 }}{{cite journal | vauthors = Zhen G, Park SW, Nguyenvu LT, Rodriguez MW, Barbeau R, Paquet AC, Erle DJ | title = IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 36 | issue = 2 | pages = 244–253 | date = February 2007 | pmid = 16980555 | pmc = 1899314 | doi = 10.1165/rcmb.2006-0180OC }} and overexpression of pendrin results in airway inflammation, hyperreactivity, and increased mucus production.{{cite journal | vauthors = Pedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, Di Candia M, Bandettini R, Ravazzolo R, Zegarra-Moran O, Galietta LJ | title = Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: role of pendrin and anion channels | journal = Journal of Immunology | volume = 178 | issue = 8 | pages = 5144–5153 | date = April 2007 | pmid = 17404297 | doi = 10.4049/jimmunol.178.8.5144 | doi-access = free }}{{cite journal | vauthors = 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 | title = Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease | journal = Journal of Immunology | volume = 180 | issue = 9 | pages = 6262–6269 | date = May 2008 | pmid = 18424749 | doi = 10.4049/jimmunol.180.9.6262 | doi-access = free }} These symptoms could result from pendrin's effects on ion concentration in the airway surface liquid, possibly causing the liquid to be less hydrated.{{cite journal | vauthors = Nakagami Y, Favoreto S, Zhen G, Park SW, Nguyenvu LT, Kuperman DA, Dolganov GM, Huang X, Boushey HA, Avila PC, Erle DJ | title = 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 = Journal of Immunology | volume = 181 | issue = 3 | pages = 2203–2210 | date = August 2008 | pmid = 18641360 | pmc = 2491716 | doi = 10.4049/jimmunol.181.3.2203 }}

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{{refend}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pendred GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4]
• [http://oto.wustl.edu/thc/innerear/pendrin-text.htm Description at oto.wustl.edu]
• {{MeshName|SLC26A4+protein,+human}}

{{Membrane transport proteins}}

{{Thyroid hormone metabolism enzymes and transporters}}

Category:Solute carrier family

Category:Thyroid

Category:Integral membrane proteins