Structure-Function Analysis of Sarcospan

描述(由申请人提供)：该项目的总体、长期目标 建议了解一种新的Tetrspanin的结构和功能 叫做萨科斯潘。萨科斯潘是 抗肌营养不良蛋白-糖蛋白复合体，在骨骼和心脏中高表达 肌肉以及许多非肌肉组织(Crosbie等人，1997；Crosbie等人 等人，1998年；Crosbie等人，1999年)。营养不良蛋白-糖蛋白复合体(DGC)是 一种跨越肌肉质膜并连接 细胞外基质和细胞内的细胞骨架。这一结构 连接对于正常的肌肉功能是至关重要的，这一点从 许多形式的肌营养不良症是由基因突变引起的 营养不良蛋白-糖蛋白复合体。几种信号分子间的相互作用 DGC也提示这个复合体可能起到调节作用 细胞外和细胞内的通讯。此外，横向联系 在DGC的膜成分中对这一功能至关重要 很复杂。假设肉毒杆菌促进蛋白质-蛋白质之间的相互作用 营养不良蛋白-糖蛋白复合体内的相互作用。这些蛋白质 相互作用显然对两国之间的物理联系很重要 细胞外基质与细胞内肌动蛋白网络及其预防 肌肉萎缩症的症状。 在已知的研究中，尚未发现sarcospan基因内的人类突变。 常染色体隐性遗传性肌营养不良症3例(Crosbie等人，2000年)。 然而，这些突变搜索只检查了普遍存在的形式的 SSPN，具有广泛的表达模式。初步数据显示， 一种新的肌肉特异形式的SSPN在骨骼和心脏中表达 肌肉。我们假设肌肉SSPN内的突变可能导致新的形式 肌肉萎缩症的症状。它的鉴定和表征 肌肉肌肉松弛疗法将促进我们对 肌营养不良蛋白-糖蛋白复合体在正常肌肉中的表达及其在糖尿病发病机制中的作用 肌肉营养不良症。

DESCRIPTION (provided by applicant): The broad, long-term objectives of this proposal are to understand the structure and function of a novel tetraspanin called SARCOSPAN. Sarcospan is an integral component of the dystrophin-glycoprotein complex and is highly expressed in skeletal and cardiac muscles, as well as many non-muscle tissues (Crosbie et al., 1997; Crosbie et al., 1998; Crosbie et al., 1999). The dystrophin-glycoprotein complex (DGC) is a structural complex that spans the muscle plasma membrane and links the extracellular matrix with the intracellular cytoskeleton. This structural linkage is critical for normal muscle function as clearly demonstrated by the many forms of muscular dystrophy that result from mutations in the dystrophin-glycoprotein complex. Association of several signaling molecules with the DGC also suggests that this complex may play a role in mediating extracellular-intracellular communications. Furthermore, lateral associations amongst membrane components of the DGC are critical for function of this complex. It is hypothesized that sarcospan facilitates protein-protein interactions within the dystrophin-glycoprotein complex. These protein interactions are clearly important for the physical linkage between the extracellular matrix and the intracellular actin network and for the prevention of muscular dystrophy. Human mutations within the sarcospan gene have not been identified in known cases of autosomal recessive muscular dystrophy (Crosbie et al., 2000). However, these mutation searches have only examined the ubiquitous form of SSPN, which has a broad expression pattern. Preliminary data demonstrates that a novel, muscle-specific form of SSPN is expressed in skeletal and cardiac muscles. We hypothesize that mutations within muscle-SSPN may cause novel forms of muscular dystrophy. Identification and characterization of this muscle-sarcospan will advance our understanding of the role of the dystrophin-glycoprotein complex in normal muscle and in the pathogenesis of muscular dystrophy.