Unusual 5′ transcript complexity of plectin isoforms:: novel tissue-specific exons modulate actin binding activity
Unusual 5′ transcript complexity of plectin isoforms:: novel tissue-specific exons modulate actin binding activity
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DOI：
10.1093/hmg/8.13.2461
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发表时间：
1999-12-01
影响因子：
3.5
通讯作者：
Wiche, G
中科院分区：
文献类型：
--
作者：
Fuchs, P;Zörer, M;Wiche, G
Plectin的翻译结果：Plectin的翻译结果：Plectin的翻译结果：Plectin是迄今为止发现的最通用的细胞连接因子，在维持皮肤、骨骼肌和心脏的机械完整性方面具有重要的功能，正如对Plectin缺乏的小鼠和人类的分析所表明的那样。Plectin在各种组织和细胞类型中的表达，结合在分子水平上发现的大量不同的结合伙伴，需要复杂的机制来调节基因转录和表达。为了研究这些机制，我们分析了小鼠plectin基因的转录多样性和基因组组织，发现其5'端结构具有显著的复杂性。发现了14个异常多的选择性剪接外显子，其中11个直接剪接到plectin外显子2上。对其组织分布的分析显示，其中一些基因的表达仅限于大脑、骨骼肌和心脏等组织。此外，我们还发现了两个短外显子组织特异性地拼接到一组高度保守的外显子中，这些外显子编码n端肌动蛋白结合域（ABD），与plectin和spectrin/dystrophin型肌动蛋白结合蛋白超家族共同。利用重组蛋白，我们发现一种新的ABD版本包含在plectin的肌肉特异性异构体中，表现出比其他剪接形式更高的肌动蛋白结合活性，这种基于选择性剪接的微调机制可能优化了plectin作为细胞连接子的生物学作用，以对抗横纹肌等组织中的强烈机械力。
Plectin, the most versatile cytolinker identified to date, has essential functions in maintaining the mechanical integrity of skin, skeletal muscle and heart, as indicated by analyses of plectin-deficient mice and humans, Expression of plectin in a vast variety of tissues and cell types, combined with a large number of different binding partners identified at the molecular level, calls for complex mechanisms regulating gene transcription and expression of the protein. To investigate these mechanisms, we analyzed the transcript diversity and genomic organization of the murine plectin gene and found a remarkable complexity of its 5'-end structure. An unusually high number of 14 alternatively spliced exons, 11 of them directly splicing into plectin exon 2, were identified. Analysis of their tissue distribution revealed that expression of a few of them is restricted to tissues such as brain, or skeletal muscle and heart. In addition, we found two short exons tissue-specifically spliced into a highly conserved set of exons encoding the N-terminal actin binding domain (ABD), common to plectin and the superfamily of spectrin/dystrophin-type actin binding proteins. Using recombinant proteins we show that a novel ABD version contained in the muscle-specific isoform of plectin exhibits significantly higher actin binding activity than other splice forms, This fine tuning mechanism based on alternative splicing is likely to optimize the proposed biological role of plectin as a cytolinker opposing intense mechanical forces in tissues like striated muscle.