A role for VAX2 in correct retinal function revealed by a novel genomic deletion at 2p13.3 causing distal Renal Tubular Acidosis: case report.

Background: Distal Renal Tubular Acidosis is a disorder of acid-base regulation caused by functional failure of α-intercalated cells in the distal nephron. The recessive form of the disease (which is usually associated with sensorineural deafness) is attributable to mutations in ATP6V1B1 or ATP6V0A4, which encode the tissue-restricted B1 and a4 subunits of the renal apical H(+)-ATPase. ATP6V1B1 lies adjacent to the gene encoding the homeobox domain protein VAX2, at 2p13.

Physical and functional links between anion exchanger-1 and sodium pump.

Anion exchanger-1 (AE1) mediates chloride-bicarbonate exchange across the plasma membranes of erythrocytes and, via a slightly shorter transcript, kidney epithelial cells. On an omnivorous human diet, kidney AE1 is mainly active basolaterally in α-intercalated cells of the collecting duct, where it is functionally coupled with apical proton pumps to maintain normal acid-base homeostasis. The C-terminal tail of AE1 has an important role in its polarized membrane residency.

Importance of early audiologic assessment in distal renal tubular acidosis.

Autosomal recessive distal renal tubular acidosis is usually a severe disease of childhood, often presenting as failure to thrive in infancy. It is often, but not always, accompanied by sensorineural hearing loss, the clinical severity and age of onset of which may be different from the other clinical features. Mutations in either ATP6V1B1 or ATP6V0A4 are the chief causes of primary distal renal tubular acidosis with or without hearing loss, although the loss is often milder in the latter.

Glyceraldehyde 3-phosphate dehydrogenase is required for band 3 (anion exchanger 1) membrane residency in the mammalian kidney.

The mammalian kidney isoform of the essential chloride-bicarbonate exchanger AE1 differs from its erythrocyte counterpart, being shorter at its N terminus. It has previously been reported that the glycolytic enzyme GAPDH interacts only with erythrocyte AE1, by binding to the portion not found in the kidney isoform. (Chu H, Low PS.

Cellular physiology of the renal H+ATPase.

Purpose Of Review: Vacuolar-type H+ATPases are multisubunit macromolecules that play an essential role in renal acid-base homeostasis. Other cellular processes also rely on the proton pumping ability of H+ATPases to acidify organellar or lumenal spaces. Several diseases, including distal renal tubular acidosis, osteoporosis and wrinkly skin syndrome, are due to mutations in genes encoding alternate subunits that make up the H+ATPase.

Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1.

The vacuolar-type ATPase (H+ATPase) is a ubiquitously expressed multisubunit pump whose regulation is poorly understood. Its membrane-integral a-subunit is involved in proton translocation and in humans has four forms, a1-a4. This study investigated two naturally occurring point mutations in a4's COOH terminus that cause recessive distal renal tubular acidosis (dRTA), R807Q and G820R.

Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component.

Several of the 13 subunits comprising mammalian H(+)-ATPases have multiple alternative forms, encoded by separate genes and with differing tissue expression patterns. These may play an important role in the intracellular localization and activity of H(+)-ATPases. Here we report the cloning of a previously uncharacterized human gene, ATP6V0E2, encoding a novel H(+)-ATPase e-subunit designated e2.