Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
FEBS J. 2013 Sep;280(17):4210-29. doi: 10.1111/febs.12295. Epub 2013 May 13.
Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.
三个黏附复合物跨越肌膜，促进细胞外基质与肌动蛋白细胞骨架之间的关键连接：dystrophin 和 utrophin-糖蛋白复合物以及 α7β1 整合素。单个蛋白成分的缺失会导致整个蛋白复合物的缺失和肌肉营养不良。肌肉营养不良是一种进行性、致命性的消耗性疾病，其特征是肌纤维反复退化和再生。蛋白质替代疗法为肌肉营养不良的治疗提供了一种很有前途的方法。最近，我们证明 sarcospan 促进黏附复合物之间的蛋白-蛋白相互作用，是一个重要的潜在治疗靶点。在这里，我们回顾了当前的蛋白质替代策略，讨论了 sarcospan 表达的潜在益处，并确定了 sarcospan 进入临床前必须解决的重要实验。
