Chloride-bicarbonate exchanger
Encyclopedia : C : CH : CHL : Chloride-bicarbonate exchanger
Introduction
Anion Exchanger 1 (AE1) or Band 3 is a phylogenetically preserved transport protein that is relatively ubiquitous throughout animal tissues. It is responsible for catalysing the electroneutral exchange of Chloride(Cl-) for Bicarbonate(HCO3-)across a plasma membrane. However, in humans it has particular significance in two specific sites, namely in the erythrocyte (red blood cell) cell membrane and on the basolateral surface of the alpha-intercalated cell (the acid secreting cell type)in the collecting duct of the kidney.The erythrocyte and kidney forms are different isoforms of the same protein.
Discovery
AE1 was discovered following gel electrophoresis of erythrocyte cell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'.AE1 in Red Cells
AE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface, indeed each red cell contains approximately one million copies of AE1. Here it performs two functions;Electroneutral chloride and bicarbonate exchange across the plasma membrane on a one-for-one basis.
Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding with ankyrin and protein 4.2).This appears to be to prevent membrane surface loss, rather than being to do with membrane skeleton assembly.
Mutations of erythroid AE1 cause between 15-25% of cases of heriditary spherocytosis (a disorder associated with progressive red cell membrane loss)
AE1 in Alpha-Intercalated cells
A different isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the basolateral surface of the alpha-intercalated cell in the collecting duct of the kidney. This is the principal acid secreting cell of the kidney, which generates hydrogen ions and bicarbonate ions from carbon dioxide and water-a reaction catalysed by Carbonic Anhydrase. The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ATPase, the apical proton pump,which thus excretes acid into the urine. kAE1 exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood.
Mutations of kidney AE1 cause distal (type1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acid.
The chloride-bicarbonate exchanger in the red cell membrane is not a pump, which would use metabolic energy. Nor is it strictly an enzyme. It is protein counter-transporter, known as band III. Ref. M.J.Hunter (1977) J.Physiol 266, 35-49.
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