PARTIAL ANKYRIN AND SPECTRIN DEFICIENCY IN SEVERE, ATYPICAL HEREDITARY SPHEROCYTOSIS
PARTIAL ANKYRIN AND SPECTRIN DEFICIENCY IN SEVERE, ATYPICAL HEREDITARY SPHEROCYTOSIS
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DOI：
10.1056/nejm198801283180407
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发表时间：
1988-01-28
影响因子：
158.5
通讯作者：
PALEK, J
中科院分区：
文献类型：
--
作者：
COETZER, TL;LAWLER, J;PALEK, J
遗传性球形红细胞增多症是溶血性贫血的一种常见形式，其临床表现、分子基础和遗传方面具有异质性。1.主要缺陷被认为存在于红细胞膜骨架中，这是一种主要由血影蛋白、肌动蛋白和在凝胶电泳上迁移为条带4.1和4.9的蛋白质（蛋白质4.1和4.9）组成的膜下网络。2.通过电子显微镜观察骨架显示了血影蛋白四聚体纤维的主要六边形晶格，该纤维连接到含有肌动蛋白和蛋白4.1和4.9.3-5的连接复合物。血影蛋白链连接到带3的胞质部分，带3是主要的整合膜蛋白。6，7此外，蛋白4.1将血影蛋白四聚体的远端连接到跨膜糖蛋白。8，9在遗传性球形红细胞增多症中已经注意到血影蛋白的定量和定性异常。在大多数患有这种疾病的患者中观察到血影蛋白的部分缺乏。10已经发现缺乏的程度与红细胞的渗透脆性和疾病的临床严重性相关。11在患有遗传性球形红细胞增多症的三种患者中已经记录了血影蛋白不能与蛋白4.1结合的缺陷。12，[13]在本文中，我们报道了两个不相关的严重的非典型遗传性球形红细胞增多症患者;在这两个患者中，红细胞膜的血影蛋白和锚蛋白含量显著降低。在试图确定这些部分蛋白质缺陷的分子基础上，我们研究了这些蛋白质的结构和功能，并研究了蛋白水解降解可能是潜在原因的可能性。我们的研究结果表明，存在于患者红细胞膜中的残余血影蛋白和锚蛋白在结构和功能上都是正常的。我们推测，减少锚蛋白含量是主要的分子缺陷，并导致叠加减少血影蛋白含量。
HEREDITARY spherocytosis is a common form of hemolytic anemia that is heterogeneous in terms of its clinical presentation, molecular basis, and inheritance. 1. The primary defect is thought to reside in the red-cell membrane skeleton, a submembranous network composed mainly of spectrin, actin, and proteins that migrate on gel electrophoresis as bands 4.1 and 4.9 (proteins 4.1 and 4.9). 2. Visualization of the skeleton by electron microscopy has revealed a primarily hexagonal lattice of fibers of spectrin tetramers linked to junctional complexes containing actin and proteins 4.1 and 4.9.3-5 The skeleton is attached to the membrane by ankyrin (protein 2.1), which connects the .beta. chain of spectrin to the cytoplasmic portion of band 3, the major integral membrane protein.6,7 In addition, protein 4.1 links the distal ends of spectrin tetramers to transmembrane glycoproteins.8,9 Quantitative and qualitative abnormalities of spectrin have been noted in hereditary spherocytosis. A partial deficiency of spectrin has been observed in a majority of patients with the disorder.10 The degree of the deficiency has been found to correlate with the osmotic fragility of the red cells and the clinical severity of the disease.11 A defect in which spectrin is unable to bind to protein 4.1 has been documented in three kindreds of patients with hereditary spherocytosis.12,13 In this paper we report on two unrelated patients with severe, atypical hereditary spherocytosis; in both, the spectrin and ankyrin contents of the red-cell membrane were markedly decreased. In an attempt to determine the molecular basis of these partial protein deficiencies, we examined the structure and function of these proteins and investigated the possibility that proteolytic degradation may be an underlying cause. Our findings indicate that the residual spectrin and ankyrin present in the patients'' red-cell membranes are structurally and functionally normal. We postulate that the diminished ankyrin content is the primary molecular defect and results in a superimposed decrease in spectrin content.