Sarcospan, the 25-kDa transmembrane component of the dystrophin-glycoprotein complex
Sarcospan, the 25-kDa transmembrane component of the dystrophin-glycoprotein complex
复制标题
DOI：
10.1074/jbc.272.50.31221
复制
发表时间：
1997-12-12
影响因子：
4.8
通讯作者：
Campbell, KP
中科院分区：
文献类型：
--
作者：
Crosbie, RH;Heighway, J;Campbell, KP
肌营养不良蛋白-糖蛋白复合物是一种跨肌膜的多亚基蛋白复合物，在肌膜下细胞骨架和细胞外基质之间形成连接。编码这种复合物蛋白质的基因中的主要突变与几种形式的肌营养不良症有关。在这里，我们报告的sarcospan，一个独特的25 kDa的成员，这个复杂的克隆和表征。拓扑算法预测，sarcospan包含四个跨膜跨螺旋与位于细胞内的N-和C-末端结构域。系统发育分析表明，sarcospan在膜中的排列以及其一级序列与tetraspan超家族的蛋白质相似。Sarcospan与肌营养不良蛋白-糖蛋白复合物共定位和共纯化，表明其是复合物的组成部分。我们还表明，sarcospan的表达显着减少肌肉与杜氏肌营养不良症患者。这表明sarcospan在膜上的定位依赖于适当的肌营养不良蛋白表达。编码sarcospan的基因定位于人类染色体12 p11.2，该基因福尔斯位于先天性眼外肌纤维化（一种常染色体显性肌营养不良症）的遗传位点内。
The dystrophin-glycoprotein complex is a multisubunit protein complex that spans the sarcolemma and forms a link between the subsarcolemmal cytoskeleton and the extracellular matrix. Primary mutations in the genes encoding the proteins of this complex are associated with several forms of muscular dystrophy. Here we report the cloning and characterization of sarcospan, a unique 25-kDa member of this complex. Topology algorithms predict that sarcospan contains four transmembrane spanning helices with both N- and C-terminal domains located intracellularly. Phylogenetic analysis reveals that sarcospan's arrangement in the membrane as well as its primary sequence are similar to that of the tetraspan superfamily of proteins. Sarcospan co-localizes and co-purifies with the dystrophin-glycoprotein complex, demonstrating that it is an integral component of the complex. We also show that sarcospan expression is dramatically reduced in muscle from patients with Duchenne muscular dystrophy. This suggests that localization of sarcospan to the membrane is dependent on proper dystrophin expression. The gene encoding sarcospan maps to human chromosome 12p11.2, which falls within the genetic locus for congenital fibrosis of the extraocular muscle, an autosomal dominant muscular dystrophy.