Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion

Abstract

Pendrin is an anion transporter encoded by the PDS͞Pds gene. In humans, mutations in PDS cause the genetic disorder Pendred syndrome, which is associated with deafness and goiter. Previous studies have shown that this gene has a relatively restricted pattern of expression, with PDS͞Pds mRNA detected only in the thyroid, inner ear, and kidney. The present study examined the distribution and function of pendrin in the mammalian kidney. Immunolocalization studies were performed using anti-pendrin polyclonal and monoclonal antibodies. Labeling was detected on the apical surface of a subpopulation of cells within the cortical collecting ducts (CCDs) that also express the H ؉ -ATPase but not aquaporin-2, indicating that pendrin is present in intercalated cells of the CCD. Furthermore, pendrin was detected exclusively within the subpopulation of intercalated cells that express the H ؉ -ATPase but not the anion exchanger 1 (AE1) and that are thought to mediate bicarbonate secretion. The same distribution of pendrin was observed in mouse, rat, and human kidney. However, pendrin was not detected in kidneys from a Pds-knockout mouse. Perfused CCD tubules isolated from alkali-loaded wild-type mice secreted bicarbonate, whereas tubules from alkali-loaded Pds-knockout mice failed to secrete bicarbonate. Together, these studies indicate that pendrin is an apical anion transporter in intercalated cells of CCDs and has an essential role in renal bicarbonate secretion.

Ion uptake and acid secretion in zebrafish (Danio rerio)

“…Another candidate for apical Cl -uptake/base secretion is pendrin (SLC26A), which is localized in the apical region of B-type intercalated cells of the cortical collecting duct and which functions in renal Cl -reabsorption and bicarbonate secretion (Royaux et al, 2001;Wagner, 2007). In the stingray (Dasyatis sabina), Piermarini and coworkers (Piermarini et al, 2002) used an anti-pendrin (SLC26A4) antibody to indicate immunoreactions in the apical region of gill ionocytes that are rich in basolateral H + -ATPase.…”

Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

“…Pendrin consists of 780 amino acids with a predicted cytoplasmic amino terminus and 12 transmembrane spanning regions (1,2). Functional studies show that pendrin mediates electroneutral exchange of Cl 2 with various anions including I 2 , HCO 3 2 , OH 2 , NO 3 2 , SCN 2 (thiocyanate), and HCO 2 2 (formate) (2)(3)(4)(5)(6)(7)(8). In addition to the inner ear and thyroid, pendrin is expressed in the kidney, airways, and adrenal gland (1,4,6,7,(9)(10)(11)(12).…”

“…In the thyroid pendrin is expressed on the apical membrane of follicular cells, where it facilitates I 2 efflux into the follicle colloid for thyroid hormone synthesis (2,15). In the kidney pendrin is expressed in the apical plasma membrane of type B and non-A/non-B intercalated cells, where it facilitates Cl 2 absorption and HCO 3 2 secretion, ABBREVIATIONS: ASL, airway surface liquid; CaCC, calcium-activated chloride channel; CF, cystic fibrosis; CFBE, human cystic fibrosis bronchial epithelial; CFTR, cystic fibrosis transmembrane conductance regulator; ENaC, epithelial sodium channel; EYFP-HIF, enhanced yellow fluorescent protein-H148Q/I152L/F46L; FRT, Fischer rat thyroid; HBE, human bronchial epithelial; IC 50 , drug concentration causing 50% inhibition; I sc , short-circuit current; PCL, periciliary layer; UCSF, University of California, San Francisco; YFP, yellow fluorescent protein although kidney abnormalities are rare in Pendred syndrome (4,6,16).…”

2007 Homer W. Smith Award

“…More recent studies showed that the apical Cl:HCO 3 exchanger is pendrin (Slc26A4) 9,10 ; hence, we have had to revise our initial hypothesis by saying that acidosis reverses the polarized distribution of only the H ϩ -ATPase, removes pendrin from the apical membrane, and induces the expression of AE1 protein and apical endocytosis.…”