Syncoilin, a novel member of the intermediate filament superfamily that interacts with α-dystrobrevin in skeletal muscle
Syncoilin, a novel member of the intermediate filament superfamily that interacts with α-dystrobrevin in skeletal muscle
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DOI：
10.1074/jbc.m008305200
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发表时间：
2001-03-02
影响因子：
4.8
通讯作者：
Blake, DJ
中科院分区：
文献类型：
--
作者：
Newey, SE;Howman, EV;Blake, DJ
肌营养不良蛋白协调正常肌肉功能所需的结构蛋白和信号蛋白的复合体的组装。Dystrophin蛋白复合体的一个关键成分是α-dystrobrevin，这是一种与dystrophin相关的蛋白，它的缺失会导致神经肌肉连接缺陷和肌肉营养不良。为了进一步了解α-dystrobrevin在骨骼肌中的作用，我们使用酵母双杂交系统来鉴定一种新的α-dystrobrevin结合伙伴，称为syncolin。Syncolin是中间细丝超家族的新成员，在骨骼肌和心肌中高度表达。在正常的骨骼肌中，syn Colin集中在神经肌肉连接处，在那里它与α-dystrobrevin-1共定位和免疫共沉淀。在哺乳动物细胞中的表达研究表明，虽然α-dystrobrevin和syncolin直接相关，但syncolin的过度表达不会导致中间细丝的自组装。最后，与dystrophin蛋白复合体的许多成分不同，我们发现在dystrophin缺陷的肌肉中，syncoiin的表达上调。这些数据表明，α-dystrobrevin在dystrophin蛋白复合体和神经肌肉连接处的中间细丝网络之间提供了联系，这可能对突触的维持和成熟起重要作用。
Dystrophin coordinates the assembly of a complex of structural and signaling proteins that are required for normal muscle function. A key component of the dystrophin protein complex is alpha -dystrobrevin, a dystrophin-associated protein whose absence results in neuromuscular junction defects and muscular dystrophy. To gain further insights into the role of alpha -dystrobrevin in skeletal muscle, we used the yeast two-hybrid system to identify a novel alpha -dystrobrevin-binding partner called syncoilin. Syncoilin is a new member of the intermediate filament superfamily and is highly expressed in skeletal and cardiac muscle. In normal skeletal muscle, syn coilin is concentrated at the neuromuscular junction, where it colocalizes and coimmunoprecipitates with alpha -dystrobrevin-1. Expression studies in mammalian cells demonstrate that, while alpha -dystrobrevin and syncoilin associate directly, overexpression of syncoilin does not result in the self-assembly of intermediate filaments. Finally, unlike many components of the dystrophin protein complex, we show that syncoiIin expression is upregulated in dystrophin-deficient muscle. These data suggest that alpha -dystrobrevin provides a link between the dystrophin protein complex and the intermediate filament network at the neuromuscular junction, which may be important for the maintenance and maturation of the synapse.