...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Mutation in the Trapα/Ssr1 Gene, Encoding Translocon-Associated Protein α, Results in Outflow Tract Morphogenetic Defects
【24h】

Mutation in the Trapα/Ssr1 Gene, Encoding Translocon-Associated Protein α, Results in Outflow Tract Morphogenetic Defects

机译：Trapα/ Ssr1基因的突变，编码与转录相关蛋白α，导致流出道形态发生缺陷。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Translocon-associated protein complex (TRAP) is thought to be required for efficient protein-specific translocation across the endoplasmic reticulum membrane. We created a mutation in the Trapα gene that leads to the synthesis of a truncated TRAPα protein fused to ShBle-β-galactosidase. Analysis of Trapα cDNAs reveals that among three different messenger RNAs expressed in the mouse, one of them encodes a slightly larger protein that differs in its C-terminal end. This mRNA, specific for skeletal muscle and heart, is only expressed after birth. Homozygous Trapα mutant pups die at birth, likely as a result of severe cardiac defects. Indeed, the septation of the proximal part of the outflow tract is absent, resulting in a double-outlet right ventricle. Studies of protein secretion in transfected embryonic fibroblasts reveal that the TRAP complex does not function properly in homozygous mutant cells and confirm, in vivo, the involvement of TRAP in substrate-specific translocation. Our results provide the first in vivo demonstration that a member of the TRAP complex plays a crucial role in mammalian heart development and suggest that TRAPα could be involved in translocation of factors necessary for maturation of endocardial cushions.
机译：Translocon相关蛋白复合物（TRAP）被认为是跨内质网膜的有效蛋白特异性转运所必需的。我们在 Trap α基因中创建了一个突变，该突变导致合成了与ShBle-β-半乳糖苷酶融合的截短的TRAPα蛋白。对 Trap αcDNA的分析表明，在小鼠中表达的三种不同信使RNA中，其中一种编码的是稍大的蛋白质，其C末端有所不同。此mRNA对骨骼肌和心脏具有特异性，仅在出生后表达。纯合的 Trap α突变幼犬在出生时死亡，可能是由于严重的心脏缺陷所致。实际上，没有流出道近端的分隔，导致右心室双出口。转染的胚胎成纤维细胞中蛋白质分泌的研究表明，TRAP复合物在纯合突变细胞中无法正常运行，并在体内证实了TRAP参与底物特异性易位。我们的结果提供了第一个体内证明TRAP复合物的成员在哺乳动物心脏发育中起关键作用的体内研究，并表明TRAPα可能参与了心内膜垫成熟所需的因子易位。

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