Ankyrin-G in skeletal muscle: Tissue-specific alternative splicing contributes to the complexity of the sarcolemmal cytoskeleton
Ankyrin-G in skeletal muscle: Tissue-specific alternative splicing contributes to the complexity of the sarcolemmal cytoskeleton
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DOI：
10.1016/j.yexcr.2005.04.013
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发表时间：
2005-09-10
影响因子：
3.7
通讯作者：
Kordeli, E
中科院分区：
文献类型：
--
作者：
Hopitzan, AA;Baines, AJ;Kordeli, E
锚蛋白是一种多功能的连接蛋白，它将基于谱蛋白的细胞骨架连接到跨膜蛋白上，并在组织细胞膜的微观结构中发挥作用。哺乳动物锚蛋白的分子多样性源于三种基因产物的广泛选择性剪接。广泛表达的Ank3基因产物ankyins - g在复杂组织中的表达多样性还没有系统的分析。我们之前描述了Ank(G107)，这是第一个肌肉特异性锚蛋白g。在这里，我们将cDNA和数据库分析结合起来，对骨骼肌的强直霉素- g有了新的认识。我们发现：(i) Ank3由至少53个外显子组成，其中许多受组织特异性剪接的影响；（ii）编码两个典型亚型(Ank（G197), Ank(G217)）和三个小亚型(Ank(G109), Ank（G128), Ank(G130)）的五个新的全长cdna使骨骼肌中表达的ankyin - g数量达到6个；（iii） c端结构域的76位残基插入是肌肉锚定蛋白的“标志”；（iv） 17/18和195个残基的可变剪接序列增加了c端结构域的多样性。内源性锚蛋白- g与体外翻译cdna的比较显示，小锚蛋白占比目鱼肌锚蛋白- g免疫反应性的大部分。当在大鼠肌肉中表达时，这些小锚蛋白都是针对肌上皮细胞的。我们的研究结果证明了骨骼肌中Ank3的组织依赖性选择性剪接，并指出了小的强直素- g在组织质膜微结构域中的新功能。(c) 2005爱思唯尔公司版权所有。
Ankyrins are versatile adaptor proteins that join the spectrin-based cytoskeleton to transmembrane proteins, and have roles in organizing the microstructure of cell membranes. Molecular diversity of ankyrins in mammals arises from extensive alternative splicing of the products of three genes. There has been no systematic analysis of the diversity of expression of ankyrins-G, the widely expressed Ank3 gene products, in a complex tissue. We previously described Ank(G107), the first muscle-specific ankyrin-G. Here, we combined cDNA and database analyses to gain novel insight into the ankyrins-G of skeletal muscle. We find: (i) that Ank3 is composed of at least 53 exons, many of which are subject to tissue-specific splicing; (ii) five novel full-length cDNAs encoding two canonical (Ank(G197), Ank(G217)) and three small isoforms (Ank(G109), Ank(G128), Ank(G130)) bring to six the number of ankyrins-G expressed in skeletal muscle; (iii) a 76-residue insert in the C-terminal domain is a 'signature' for muscle ankyrins; (iv) variably spliced sequences of 17/18 and 195 residues increase diversity in the C-terminal domains. Comparison of endogenous ankyrins-G with in vitro translated cDNAs revealed that small ankyrins account for the majority of the immunoreactivity for ankyrin-G in soleus muscle. The small ankyrins, when expressed in vivo in the rat muscle, are all targeted to sarcolemmal costameres. Our results demonstrate the tissue-dependent alternative splicing of Ank3 in skeletal muscle and point to novel functions of small ankyrins-G in organizing microdomains of the plasma membrane. (c) 2005 Elsevier Inc. All rights reserved.