van der Ven Peter F M, Ehler Elisabeth, Vakeel Padmanabhan, Eulitz Stefan, Schenk Jörg A, Milting Hendrik, Micheel Burkhard, Fürst Dieter O
Department of Molecular Cell Biology, University of Bonn, Ulrich-Haberland-Str. 61a, D-53121 Bonn, Germany.
Exp Cell Res. 2006 Jul 1;312(11):2154-67. doi: 10.1016/j.yexcr.2006.03.015. Epub 2006 Apr 24.
Filamin c is the predominantly expressed filamin isoform in striated muscles. It is localized in myofibrillar Z-discs, where it binds FATZ and myotilin, and in myotendinous junctions and intercalated discs. Here, we identify Xin, the protein encoded by the human gene 'cardiomyopathy associated 1' (CMYA1) as filamin c binding partner at these specialized structures where the ends of myofibrils are attached to the sarcolemma. Xin directly binds the EVH1 domain proteins Mena and VASP. In the adult heart, Xin and Mena/VASP colocalize with filamin c in intercalated discs. In cultured cardiomyocytes, the proteins also localize in the nonstriated part of myofibrils, where sarcomeres are assembled and an extensive reorganization of the actin cytoskeleton occurs. Unusual intraexonic splicing events result in the existence of three Xin isoforms that associate differentially with its ligands. The identification of the complex filamin c-Xin-Mena/VASP provides a first glance on the role of Xin in the molecular mechanisms involved in developmental and adaptive remodeling of the actin cytoskeleton during cardiac morphogenesis and sarcomere assembly.
细丝蛋白C是横纹肌中主要表达的细丝蛋白异构体。它定位于肌原纤维的Z线，在那里它与FATZ和肌联蛋白结合，也存在于肌-腱连接和闰盘中。在这里，我们鉴定出由人类基因“心肌病相关1”（CMYA1）编码的蛋白质Xin是细丝蛋白C在这些肌原纤维末端附着于肌膜的特殊结构处的结合伴侣。Xin直接结合EVH1结构域蛋白Mena和VASP。在成年心脏中，Xin和Mena/VASP与细丝蛋白C在闰盘中共定位。在培养的心肌细胞中，这些蛋白质也定位于肌原纤维的非横纹部分，即肌节组装和肌动蛋白细胞骨架广泛重组的部位。不寻常的外显子内剪接事件导致存在三种Xin异构体，它们与配体的结合方式不同。细丝蛋白C-Xin-Mena/VASP复合物的鉴定初步揭示了Xin在心脏形态发生和肌节组装过程中肌动蛋白细胞骨架的发育和适应性重塑所涉及的分子机制中的作用。
