Straub V, Ettinger A J, Durbeej M, Venzke D P, Cutshall S, Sanes J R, Campbell K P
Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
J Biol Chem. 1999 Sep 24;274(39):27989-96. doi: 10.1074/jbc.274.39.27989.
The sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that epsilon-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with beta- and delta-sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle sarcoglycan complex, whereas the complex was unaffected in alpha-sarcoglycan null mice in agreement with the finding that alpha-sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing epsilon-sarcoglycan, was fully restored following intramuscular injection of recombinant delta-sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the sarcoglycan complex and show that epsilon-sarcoglycan replaces alpha-sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in sarcoglycan-deficient patients.
肌聚糖复合物在横纹肌中已有充分的特征描述，其组分缺陷与肌肉萎缩症和心肌病相关。在此，我们对平滑肌肌聚糖复合物进行了特征描述。通过检查胚胎肌肉谱系和生化分级分离研究，我们证明ε-肌聚糖是平滑肌肌聚糖复合物的一个组成部分，与β-和δ-肌聚糖一起。对基因定义的肌肉萎缩症动物模型的分析支持了这一结论。缺乏δ-肌聚糖的心肌病仓鼠以及同时缺乏抗肌萎缩蛋白和抗肌萎缩蛋白聚糖的小鼠显示出平滑肌肌聚糖复合物的缺失，而在α-肌聚糖基因敲除小鼠中该复合物未受影响，这与α-肌聚糖在平滑肌细胞中不表达的发现一致。在心肌病仓鼠中，通过肌肉内注射重组δ-肌聚糖腺病毒后，含有ε-肌聚糖的平滑肌肌聚糖复合物完全恢复。总之，这些结果证明了肌聚糖复合物存在组织依赖性变异，并表明ε-肌聚糖取代α-肌聚糖作为平滑肌抗肌萎缩蛋白-糖蛋白复合物的一个组成部分。我们的结果还提示了肌聚糖缺陷患者中可能存在的平滑肌功能障碍差异的分子基础。
