Pendrin, is an anion exchangeprotein that in humans is encoded by the SLC26A4gene (solute carrier family 26, member 4).[1][2]
Pendrin was initially identified as a sodium-independent chloride-iodine exchanger[3] with subsequent studies showing that it also accepts formate and bicarbonate as substrates.[4][5] Pendrin is similar to the Band 3transport 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]
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.
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]
Clinical significance
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]
↑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. PMID10192399.
↑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. PMID10644529.
↑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. PMID11208611.
↑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. PMID22116361.
↑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. ISBN978-0-470-02957-2. PMID17120771.
↑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. PMID18538122.
↑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. PMID16083784.
↑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. PMID17404297.
↑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. PMID18424749.
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