%0 Journal Article
%T Band 3 Missense Mutations and Stomatocytosis: Insight into the Molecular Mechanism Responsible for Monovalent Cation Leak
%A Damien Barneaud-Rocca
%A Bernard Pellissier
%A Franck Borgese
%A H¨¦l¨¨ne Guizouarn
%J International Journal of Cell Biology
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/136802
%X Missense mutations in the erythroid band 3 protein (Anion Exchanger 1) have been associated with hereditary stomatocytosis. Features of cation leaky red cells combined with functional expression of the mutated protein led to the conclusion that the AE1 point mutations were responsible for and leak through a conductive mechanism. A molecular mechanism explaining mutated AE1-linked stomatocytosis involves changes in AE1 transport properties that become leaky to and . However, another explanation suggests that point-mutated AE1 could regulate a cation leak through other transporters. This short paper intends to discuss these two alternatives. 1. Introduction Band 3 or anion exchanger 1 (AE1) is the major red cell membrane protein. It belongs to the Solute Carrier 4A family (SLC4A) grouping bicarbonate transporters [1¨C3]. This protein catalyzes electroneutral chloride-bicarbonate exchange, and it is also expressed in kidney ¦Á-intercalated cells and in cardiomyocytes [4, 5]. In red cells, it is involved in two main tasks: enhancement of carbon dioxide transport and structuration of cell shape. It is found in red cells from all vertebrates except lampreys which naturally do not express erythrocyte AE1 [6]. Besides this exception, its complete absence from mammalian red cells leads to red cell defects whose consequences on health depend on the species. Dyserythropoiesis, severe haemolytic anaemia, and often premature death have been reported in mouse [7], and human [8], whereas cow or zebra fish seems to better withstand red cell AE1 deficiency [9, 10]. In human, many different mutations in SLC4A1 gene coding for AE1 have been reported [11]. Some of them are asymptomatic, whereas some others are associated with red cell pathologies characterized by alteration of red cell shape and rheological properties. As this protein is also expressed in kidney, a renal phenotype can be associated with SLC4A1 mutations. In this paper we will focus on red cell AE1, and the reader interested in kidney AE1 is therefore addressed to very exhaustive recent reviews on this subject [12¨C15]. When a red cell phenotype is associated with SLC4A1 mutations, the symptoms are hyperhaemolysis and anaemia, icterus, and splenomegaly. However, these symptoms may vary widely in intensity. It appears that the SLC4A1 mutations can be divided into two classes according to the way they impair AE1 function: (1) those that prevent correct folding of the protein so that it is not addressed to plasma membrane. This leads to a lower amount of AE1 in red cell membrane that impairs connection of
%U http://www.hindawi.com/journals/ijcb/2011/136802/