Proteolysis of β-dystroglycan in muscular diseases
Proteolysis of β-dystroglycan in muscular diseases
复制标题
DOI：
10.1016/j.nmd.2005.01.007
复制
发表时间：
2005-05-01
影响因子：
2.8
通讯作者：
Shimizu, T
中科院分区：
文献类型：
--
作者：
Matsumura, K;Zhong, D;Shimizu, T
a-三聚糖聚糖是一种结合细胞外基质（ECM）的细胞表面外周膜蛋白，而β -三聚糖聚糖是一种I型整体膜蛋白，通过n端胞外结构域将a-三聚糖聚糖锚定在细胞膜上。由α -和β -三聚糖聚糖组成的复合物称为三聚糖聚糖复合物。我们以前报道过基质金属蛋白酶（MMP）的活性，它通过切割β -三磷酸腺苷的细胞外结构域来破坏三磷酸腺苷复合物。该MMP产生一个30 kDa的β -三磷酸腺苷异常片段，该片段被针对β -三磷酸腺苷异常c端的单克隆抗体43DAG/8D5检测到。我们还报道了心肌病仓鼠（肌糖病的模型动物）的骨骼肌和心肌中β -糖异常蛋白的30 kDa片段增加，这导致通过糖异常蛋白复合物破坏了ECM和细胞膜之间的联系。在这项研究中，我们研究了各种人类肌肉疾病（包括肌糖病、杜氏肌营养不良症（DMD）、贝克肌营养不良症、福山先天性肌营养不良症、三吉肌病、LGMD2A、面舟状肌营养不良症、肌强直性营养不良症和皮肌炎/多发性肌炎）活检骨骼肌中β -肌营养不良蛋白的蛋白水解。我们发现30 kDa的β -糖异常蛋白片段在肌糖病和DMID中显著增加，但在其他疾病中没有。我们认为，肌糖病和DMD中β -肌糖异常蛋白的蛋白水解可能通过破坏肌外基质和细胞膜之间的联系而导致骨骼肌变性。(c) 2005 Elsevier B.V.版权所有
a-Dystroglycan is a cell surface peripheral membrane protein which binds to the extracellular matrix (ECM), while beta-dystroglycan is a type I integral membrane protein which anchors a-dystroglycan to the cell membrane via the N-terminal extracellular domain. The complex composed of alpha-and beta-dystroglycan is called the dystroglycan complex. We reported previously a matrix metalloproteinase (MMP) activity that disrupts the dystroglycan complex by cleaving the extracellular domain of beta-dystroglycan. This MMP creates a characteristic 30 kDa fragment of beta-dystroglycan that is detected by the monoclonal antibody 43DAG/8D5 directed against the C-terminus of beta-dystroglycan. We also reported that the 30 kDa fragment of beta-dystroglycan was increased in the skeletal and cardiac muscles of cardiornyopathic hamsters, the model animals of sarcoglycanopathy, and that this resulted in the disruption of the link between the ECM and cell membrane via the dystroglycan complex. In this study, we investigated the proteolysis of beta-dystroglycan in the biopsied skeletal muscles of various human muscular diseases, including sarcoglycanopathy, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, Fukuyama congenital muscular dystrophy, Miyoshi myopathy, LGMD2A, facioscapulolmmeral muscular dystrophy, myotonic dystrophy and dermatomyositis/polymyositis. We show that the 30 kDa fragment of beta-dystroglycan is increased significantly in sarcoglycanopathy and DMID, but not in the other diseases. We propose that the proteolysis of beta-dystroglycan may contribute to skeletal muscle degeneration by disrupting the link between the ECM and cell membrane in sarcoglycanopathy and DMD. (c) 2005 Elsevier B.V. All rights reserved.