Glycophorin A: Band 3 aid

Band 3 (B3) is a major site of cytoskeletal attachment to the erythrocyte membrane and is important for gas exchange. A truncated isoform of B3 (kB3) is expressed in the a-intercalated cells of the kidney and its functional activity and basolateral localization are essential for acid secretion. B3 mutations generally lead to red blood cell (RBC) specific disease (hereditary spherocytosis (HS), Southeast Asian Ovalocytosis or hereditary stomatocytosis) or kidney disease (distal Renal Tubular Acidosis-dRTA). It is rare for both the RBC and kidney disease phenotypes to co-exist, but this does occur in knockout mice, and also in humans (B3 Coimbra and B3 Courcouronne) or cattle with homozygous HS mutations. This is because RBCs express a B3 chaperone-like molecule in the form of Glycophorin A that can rescue the majority of B3 mutations that cause dRTA but probably not the majority of HS mutations. The study of naturally occurring B3 variant blood and expression of B3 or kB3 mutants in heterologous expression systems has provided valuable information concerning B3 trafficking and interactions in the RBC and kidney. This article will review these studies and comment on our current understanding of the interaction between GPA with B3 and also on the proposed B3 centred macrocomplex. (C) 2008 Elsevier Inc. All rights reserved.