Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy.
Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy.
复制标题
Zeta-肌聚糖是肌聚糖复合物的一种新成分，在肌营养不良症中减少。
DOI：
10.1093/hmg/11.18.2147
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发表时间：
2002
影响因子：
3.5
通讯作者：
McNally,ElizabethM
中科院分区：
文献类型：
--
作者：
Wheeler,MatthewT;Zarnegar,Sara;McNally,ElizabethM
肌营养不良蛋白糖蛋白复合物 (DGC) 存在于肌肉细胞的质膜上，它在细胞骨架和细胞外基质之间提供了联系。 DGC 内的一个子复合物——肌聚糖复合物，与肌营养不良蛋白结合并介导肌肉膜稳定性。肌聚糖基因突变会导致人类和小鼠的肌营养不良和心肌病。在无脊椎动物中，存在三个肌聚糖基因，而在哺乳动物中，还有可能由基因复制事件产生的额外肌聚糖基因。我们发现了一种新型哺乳动物肌聚糖，δ-肌聚糖，它与 γ-肌聚糖和 δ-肌聚糖高度相关。我们生成了 δ-肌聚糖特异性抗体，并发现 δ-肌聚糖与质膜上肌聚糖复合物的其他成员相关。此外，在肌营养不良症中，细胞膜上的 δ-肌聚糖减少，这与介导膜稳定性的作用一致。 δ-肌聚糖也被发现是血管平滑肌肌聚糖复合物的组成部分。总之，这些数据表明，δ-肌聚糖是肌聚糖复合物的一个组成部分，因此在肌营养不良症的发病机制中很重要。
The dystrophin glycoprotein complex (DGC) is found at the plasma membrane of muscle cells, where it provides a link between the cytoskeleton and the extracellular matrix. A subcomplex within the DGC, the sarcoglycan complex, associates with dystrophin and mediates muscle membrane stability. Mutations in sarcoglycan genes lead to muscular dystrophy and cardiomyopathy in both humans and mice. In invertebrates, there are three sarcoglycan genes, while in mammals there are additional sarcoglycan genes that probably arose from gene duplication events. We identified a novel mammalian sarcoglycan, ζ-sarcoglycan, that is highly related to γ-sarcoglycan and δ-sarcoglycan. We generated a ζ-sarcoglycan-specific antibody and found that ζ-sarcoglycan associated with other members of the sarcoglycan complex at the plasma membrane. Additionally, ζ-sarcoglycan was reduced at the membrane in muscular dystrophy, consistent with a role in mediating membrane stability. ζ-Sarcoglycan was also found as a component of the vascular smooth muscle sarcoglycan complex. Together, these data demonstrate that ζ-sarcoglycan is an integral component of the sarcoglycan complex and, as such, is important in the pathogenesis of muscular dystrophy.