• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles.
【24h】

Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles.

机译：钙蛋白酶3在骨骼肌肌质网中的非蛋白水解功能。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mutations in CAPN3/Capn3, which codes for skeletal muscle-specific calpain-3/p94 protease, are responsible for limb-girdle muscular dystrophy type 2A. Using knock-in is replaced with a mutant calpain-3:C129S, which is a proteolytically inactive but structurally intact calpain-3, we demonstrated in our previous studies that loss of calpain-3 protease activity causes muscular dystrophy [Ojima, K. et al. (2010) J. Clin. Invest. 120, 2672-2683]. However, compared to Capn3-null (Capn3(-/-)) mice, Capn3(CS/CS) mice showed less severe dystrophic symptoms. This suggests that calpain-3 also has a non-proteolytic function. This study aimed to elucidate the non-proteolytic functions of calpain-3 through comparison of Capn3(CS/CS) mice with Capn3(-/-) mice. We found that calpain-3 is a component of the sarcoplasmic reticulum (SR), and that calpain-3 interacts with, but does not proteolyze, typical SR components such as ryanodine receptor and calsequestrin. Furthermore, Capn3(CS/CS) mice showed that the nonenzymatic role of calpain-3 is required for proper Ca(2+) efflux from the SR to cytosol during muscle contraction. These results indicate that calpain-3 functions as a nonenzymatic element for the Ca(2+) efflux machinery in the SR, rather than as a protease. Thus, defects in the nonenzymatic function of calpain-3 must also be involved in the pathogenesis of limb-girdle muscular dystrophy type 2A.
机译：CAPN3 / Capn3中的突变编码2A型肢带肌营养不良症，该突变编码骨骼肌特异性calpain-3 / p94蛋白酶。使用敲入取代了突变的calpain-3：C129S，后者是一种蛋白水解失活但结构完整的calpain-3，我们在先前的研究中证明了calpain-3蛋白酶活性的丧失会导致肌营养不良[Ojima，K.等。等（2010）J.Clin。投资。 120，2672-2683]。但是，与Capn3-null（Capn3（-/-））小鼠相比，Capn3（CS / CS）小鼠显示出较轻的营养不良症状。这表明钙蛋白酶3也具有非蛋白水解功能。这项研究旨在通过比较Capn3（CS / CS）小鼠与Capn3（-/-）小鼠来阐明calpain-3的非蛋白水解功能。我们发现，钙蛋白酶3是肌浆网（SR）的组成部分，并且钙蛋白酶3与典型的SR组分（如莱诺丹碱受体和钙硒蛋白）相互作用，但不会蛋白水解。此外，Capn3（CS / CS）小鼠显示钙蛋白酶3的非酶作用是肌肉收缩期间从SR到胞质溶胶的适当Ca（2+）外排所必需的。这些结果表明，钙蛋白酶3充当SR中Ca（2+）外排机制的非酶元素，而不是蛋白酶。因此，calpain-3的非酶功能缺陷也必须与2A型肢带型肌营养不良症的发病机理有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号