Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain
Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain
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DOI：
10.1074/jbc.m010418200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Blake, DJ
中科院分区：
文献类型：
--
作者：
Benson, MA;Newey, SE;Blake, DJ
肌营养不良蛋白相关蛋白复合物（DPC）是维持肌肉完整性所必需的，在收缩和松弛的机械应力。除了提供膜支架外，DPC的成员如α-肌营养不良蛋白蛋白家族被认为在细胞内信号转导中起重要作用。为了进一步了解DPC的功能，我们进行了酵母双杂交筛选肌养蛋白相互作用蛋白。在这里，我们描述了一个dysbindin，一种新的肌营养不良结合蛋白结合蛋白的鉴定。Dysbindin是一种进化上保守的含有40-kDa卷曲螺旋的蛋白质，其结合肌肉和脑中的α-和β-肌养短蛋白。肌营养不良蛋白和α-短肌养蛋白与dysbindin共免疫沉淀，表明dysbindin在肌肉中是DPC相关的。Dysbindin与α-肌养短蛋白共定位于肌膜处，并且在肌养蛋白缺陷的肌肉中上调。在脑中，dysbindin主要存在于轴突束中，特别是某些轴突末端，特别是小脑和海马中的杂乱纤维突触末端。这些发现对Duchenne型肌营养不良症的分子病理学有影响，并可能为将短肌营养不良蛋白和DPC锚定到肌膜提供另一种途径。
The dystrophin-associated protein complex (DPC) is required for the maintenance of muscle integrity during the mechanical stresses of contraction and relaxation. In addition to providing a membrane scaffold, members of the DPC such as the alpha -dystrobrevin protein family are thought to play an important role in intracellular signal transduction. To gain additional insights into the function of the DPC, we performed a yeast two-hybrid screen for dystrobrevin-interacting proteins. Here we describe the identification of a dysbindin, a novel dystrobrevin-binding protein. Dysbindin is an evolutionary conserved 40-kDa coiled-coil-containing protein that binds to alpha- and beta -dystrobrevin in muscle and brain. Dystrophin and alpha -dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin co-localizes with alpha -dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon bundles and especially in certain axon terminals, notably messy fiber synaptic terminals in the cerebellum and hippocampus. These findings have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.