Pendrin is ananion exchangeprotein that in humans is encoded by theSLC26A4gene (solute carrier family 26, member 4).[5][6]Pendrin was initially identified as a sodium-independent chloride-iodide exchanger[7] with subsequent studies showing that it also acceptsformate andbicarbonate as substrates.[8][9] Pendrin is similar to theBand 3transport protein found inred blood cells. Pendrin is the protein which is mutated inPendred syndrome, which is an autosomal recessive disorder characterized by sensorineural hearing loss,goiter and a partial organification problem detectable by a positive perchlorate test.[10]
Byphylogenetic analysis, pendrin has been found to be a close relative ofprestin 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.
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.[11]
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[13][14] or indirectly modulate the calcium concentration of the endolymph.[15] Pendrin is also expressed in the kidney, and has been localized to the apical membrane of a population of intercalated cells in thecortical collecting duct where it is involved in bicarbonate secretion.[16][17]
Renalβ-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.[18]
Mutations in this gene are associated withPendred syndrome, the most common form of syndromicdeafness, 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.[19] SLC26A4 is highly homologous to theSLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters.[5]
Another little-understood role of pendrin is in airway hyperreactivity andinflammation, as during asthma attacks and allergic reactions. Expression of pendrin in the lung increases in response to allergens and high concentrations ofIL-13,[20][21] and overexpression of pendrin results in airway inflammation, hyperreactivity, and increased mucus production.[22][23] These symptoms could result from pendrin's effects on ion concentration in the airway surface liquid, possibly causing the liquid to be less hydrated.[24]
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^Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, et al. (February 2001). "Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex".American Journal of Physiology. Renal Physiology.280 (2):F356 –F364.doi:10.1152/ajprenal.2001.280.2.f356.PMID11208611.
^Kessler J, Obinger C, Eales G (July 2008). "Factors influencing the study of peroxidase-generated iodine species and implications for thyroglobulin synthesis".Thyroid.18 (7):769–774.doi:10.1089/thy.2007.0310.PMID18631006.
^Wall SM (2006). "The Renal Physiology of Pendrin (SLC26A4) and Its Role in Hypertension".Epithelial Anion Transport in Health and Disease: The Role of the SLC26 Transporters Family. Novartis Foundation Symposia. Vol. 273. pp. 231–9, discussion 239–43,261–4.doi:10.1002/0470029579.ch15.ISBN978-0-470-02957-2.PMID17120771.
^Koeppen BM, Stanton BA, Swiatecka-Urban A, eds. (2024).Berne & Levy Physiology (8th ed.). Philadelphia, PA: Elsevier.ISBN978-0-323-84790-2.
^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):450–453.doi:10.5414/cnp69450.PMID18538122.
^Kuperman DA, Lewis CC, Woodruff PG, Rodriguez MW, Yang YH, Dolganov GM, et al. (August 2005). "Dissecting asthma using focused transgenic modeling and functional genomics".The Journal of Allergy and Clinical Immunology.116 (2):305–311.doi:10.1016/j.jaci.2005.03.024.PMID16083784.
Baldwin CT, Weiss S, Farrer LA, De Stefano AL, Adair R, Franklyn B, et al. (September 1995). "Linkage of congenital, recessive deafness (DFNB4) to chromosome 7q31 and evidence for genetic heterogeneity in the Middle Eastern Druze population".Human Molecular Genetics.4 (9):1637–1642.doi:10.1093/hmg/4.9.1637.PMID8541853.
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