#EB2012: A Pendrin for Your Thoughts

Apr 23 2012 Published by under [Biology&Environment], EB2012 Meeting

Pendrin, also known as SLC26A4, is a luminal anion transporter. Anions, molecules with a negative charge, include chloride, bicarbonate, iodide, and others. The family of similar transporters (see figure) have some functional overlap, although knock-out studies confirm some individual transport specificities.

A child that lacks pendrin has Pendred Syndrome. This usually occurs as a monogenic recessive disorder (both parents have a mutation in the pendrin gene) although a few families have a digenic inheritance where the mutation occurs in a gene that controls the creation or function of pendrin. The major manifestation of the syndrome is progressive hearing loss; this syndrome may produce as much as 10% of congenital familial deafness. The syndrome also causes enlargement of portions of the inner ear and an enlarged thyroid gland (or goiter). The function of the thyroid remains normal, but it accumulates material and grows.

After Richard J. H. Smith reviewed the features and genetics of the syndrome, Philene Wangemann showed the role of pendrin in ear development in mice.

Click to enlarge

Using conditional knock-outs of the gene, her group has established a critical 2-day period in gestation where lack of pendrin results in deafness. The mice also develop enlargement of the cochlea, just like humans. For her review on pendrin in ear development click here (PDF is free!).

So why does the thyroid enlarge in this syndrome? For those of you who are not endocrinologists (I may not be one, but I do sleep with one), thyroid hormone contains iodine.That's why a low iodine diet so profoundly affects growth and development (AKA cretinism). Since this family of transporters helps move iodine about, the thyroid can enlarge, even though its ability to make and release the hormone is intact. This topic was addressed by Peter Kopp.

Finally (saving the best for last?) Vladimir Pech reviewed the role of pendrin in blood pressure regulation. Pendrin resides in the type B intercalated cells of the cortical collecting duct where it exchanges chloride and bicarbonate between the lumen and the cell. Pendrin knock-out mice have normal blood pressures; however, during states where aldosterone would be activated (low sodium and low volume), pendrin mice are unable to conserve sodium as avidly as those with the transporter.

Huh? Most aldosterone-dependent sodium reabsorption occurs via the ENaC channel in the principal cell. How does a lack of pendrin tell another cell to behave differently? It does so by decreasing the activation of ENaC which requires a cleavage step to work. Perhaps this occurs via altered luminal pH or bicarbonate concentration, or some other signal that impairs the milieu for sodium channel activation. More to come; click here for a nice review (unfortunately not available freely online).

Ear and kidney abnormalities often occur together in children. Pendrin may provide one link to explain some of these issues.

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