Pendrin is an
anion exchange protein that in humans is encoded by the ''SLC26A4''
gene (solute carrier family 26, member 4).
Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studies showing that it also accepts
formate
Formate (IUPAC name: methanoate) is the conjugate base of formic acid. Formate is an anion () or its derivatives such as ester of formic acid. The salts and esters are generally colorless.Werner Reutemann and Heinz Kieczka "Formic Acid" in ''Ull ...
and
bicarbonate as substrates. 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.
Pendrin is responsible for mediating the
electroneutral exchange
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively permeable membrane, selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of ...
of
chloride (Cl
−) for bicarbonate (HCO
3−) across a
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
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
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. 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 or indirectly modulate the calcium concentration of the endolymph. 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.
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. SLC26A4 is highly homologous to the
SLC26A3
Chloride anion exchanger, also known as down-regulated in adenoma (protein DRA), is a protein that in humans is encoded by the ''SLC26A3'' gene.
Function
Protein DRA is a membrane protein in intestinal cells. It is an anion exchanger and a me ...
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,
and overexpression of pendrin results in airway inflammation, hyperreactivity, and increased mucus production.
These symptoms could result from pendrin's effects on ion concentration in the airway surface liquid, possibly causing the liquid to be less hydrated.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4*
{{Thyroid hormone metabolism enzymes and transporters
Solute carrier family
Thyroid
Integral membrane proteins