Tissue-specific alternative splicing of protein 4.1 inserts an exon necessary for formation of the ternary complex with erythrocyte spectrin and F-actin.
Tissue-specific alternative splicing of protein 4.1 inserts an exon necessary for formation of the ternary complex with erythrocyte spectrin and F-actin.
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DOI：
10.1182/blood.v82.8.2558.2558
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发表时间：
1993-10
期刊：
影响因子：
20.3
通讯作者：
WC Horne;SC Huang;PS Becker;TK Tang;EJ Jr Benz
中科院分区：
文献类型：
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作者：
WC Horne;SC Huang;PS Becker;TK Tang;EJ Jr Benz
红细胞蛋白4.1是一种78- 80-Kd的外周膜蛋白，其促进血影蛋白与肌动蛋白原丝的相互作用，并将所得的联锁网络连接到整合的膜蛋白。有几种蛋白4.1的亚型似乎在一组有限的组织中表达。这些产生于可变的mRNA剪接事件，其导致成熟mRNA内至少10个核苷酸（基序）块的组合插入或缺失。其中之一，基序I，由63个核苷酸编码21个氨基酸的N-末端区域的假定血影蛋白/肌动蛋白结合域。含U基序同种型的表达发生在红系成熟的晚期。我们产生了重组亚型的蛋白质4.1和推定的10-Kd血影蛋白/肌动蛋白结合片段，含有或缺乏这21个氨基酸序列，并检查他们的能力，形成一个三元复合物与红细胞血影蛋白和F-肌动蛋白。完整蛋白质和含有基序I编码的序列的10-Kd片段的同种型有效地形成三元复合物。缺乏该序列但在其他方面相同的同种型不参与三元复合物的形成。这些结果，结合基序I在红细胞成熟后期的表达，表明与肌动蛋白和血影蛋白的红细胞形式的相互作用是红细胞形式的蛋白4.1的一个专门的属性。因此，发育中的红细胞中的mRNA剪接在高度特化的红细胞膜的形成中起着关键的适应性作用。
Erythrocyte protein 4.1 is an 78- to 80-Kd peripheral membrane protein that promotes the interaction of spectrin with actin protofilaments and links the resulting interlocking network to the integral membrane proteins. There are several isoforms of protein 4.1 that appear to be expressed in a restricted group of tissues. These arise from alternative mRNA splicing events that lead to the combinational insertion or deletion of at least 10 blocks of nucleotides (motifs) within the mature mRNA. One of these, motif I, consists of 63 nucleotides encoding 21 amino acids in the N-terminal region of the putative spectrin/actin-binding domain. The expression of the motif U-containing isoform occurs late in erythroid maturation. We generated recombinant isoforms of protein 4.1 and of the putative 10-Kd spectrin/actin-binding fragment that contain or lack this 21 amino acid sequence and examined their ability to form a ternary complex with erythrocyte spectrin and F-actin. The isoforms of the complete protein and of the 10-Kd fragment that contain the sequence encoded by motif I efficiently form the ternary complex. Isoforms that lack this sequence, but are otherwise identical, do not participate in the formation of the ternary complex. These results, in conjunction with the expression of motif I during late erythroid maturation, suggest that interaction with actin and the erythroid form of spectrin is a specialized property of the erythrocyte form of protein 4.1. Alternative mRNA splicing in developing red blood cells thus plays a key adaptive role in the formation of the highly specialized erythrocyte membrane.