Yang B, Jung D, Motto D, Meyer J, Koretzky G, Campbell K P
Howard Hughes Medical Institute, College of Medicine, Iowa City, Iowa, USA.
J Biol Chem. 1995 May 19;270(20):11711-4. doi: 10.1074/jbc.270.20.11711.
Dystroglycan is a novel laminin receptor that links the extracellular matrix and sarcolemma in skeletal muscle. The dystroglycan complex containing alpha- and beta-dystroglycan also serves as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. beta-Dystroglycan has now been expressed in vitro and shown to directly interact with Grb2, an adapter protein involved in signal transduction and cytoskeletal organization. Protein binding assays with two Grb2 mutants, Grb2/P49L and Grb2/G203R, which correspond to the loss-of-function mutants in the Caenorhabditis elegans sem-5, demonstrated that the dystroglycan-Grb2 association is through beta-dystroglycan C-terminal proline-rich domains and Grb2 Src homology 3 domains. Affinity chromatography has also shown endogenous skeletal muscle Grb2 interacts with beta-dystroglycan. Immunoprecipitation experiments have demonstrated that Grb2 associates with alpha/beta-dystroglycan in vivo in both skeletal muscle and brain. The specific dystroglycan-Grb2 interaction may play an important role in extracellular matrix-mediated signal transduction and/or cytoskeleton organization in skeletal muscle that may be essential for muscle cell viability.
肌营养不良聚糖是一种新型层粘连蛋白受体，它连接骨骼肌中的细胞外基质和肌膜。包含α-和β-肌营养不良聚糖的肌营养不良聚糖复合物在肌肉中也作为聚集蛋白受体，在那里它可能调节聚集蛋白诱导的神经肌肉接头处乙酰胆碱受体的聚集。β-肌营养不良聚糖现已在体外表达，并显示与Grb2直接相互作用，Grb2是一种参与信号转导和细胞骨架组织的衔接蛋白。用两种Grb2突变体Grb2/P49L和Grb2/G203R进行的蛋白质结合试验，它们对应于秀丽隐杆线虫sem-5中的功能丧失突变体，结果表明肌营养不良聚糖与Grb2的结合是通过β-肌营养不良聚糖的C末端富含脯氨酸的结构域和Grb2的Src同源3结构域。亲和层析也表明内源性骨骼肌Grb2与β-肌营养不良聚糖相互作用。免疫沉淀实验表明，Grb2在体内与骨骼肌和大脑中的α/β-肌营养不良聚糖结合。特定的肌营养不良聚糖与Grb2的相互作用可能在细胞外基质介导的信号转导和/或骨骼肌的细胞骨架组织中起重要作用，这可能对肌肉细胞的存活至关重要。
