Williamson Rosalind C, Toye Ashley M
University of Bristol, Department of Biochemistry, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK.
Blood Cells Mol Dis. 2008 Jul-Aug;41(1):35-43. doi: 10.1016/j.bcmd.2008.01.001. Epub 2008 Mar 4.
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 alpha-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.
带3（B3）是细胞骨架附着于红细胞膜的主要位点，对气体交换很重要。B3的一种截短异构体（kB3）在肾脏的α-闰细胞中表达，其功能活性和基底外侧定位对酸分泌至关重要。B3突变通常导致红细胞（RBC）特异性疾病（遗传性球形红细胞增多症（HS）、东南亚椭圆形红细胞增多症或遗传性口形红细胞增多症）或肾脏疾病（远端肾小管酸中毒——dRTA）。红细胞和肾脏疾病表型同时存在的情况很少见，但在基因敲除小鼠中确实会出现，在人类（B3科英布拉型和B3库尔库罗讷型）或具有纯合HS突变的牛中也会出现。这是因为红细胞以血型糖蛋白A的形式表达一种B3伴侣样分子，它可以挽救大多数导致dRTA的B3突变，但可能无法挽救大多数HS突变。对天然存在的B3变异血液的研究以及在异源表达系统中B3或kB3突变体的表达，为有关B3在红细胞和肾脏中的运输及相互作用提供了有价值的信息。本文将综述这些研究，并对我们目前对GPA与B3之间相互作用的理解以及提出的以B3为中心的大复合体进行评述。
