通过减缓翻译速度以匹配限制ER向位点,SRP保持了聚酸的转位能力
Asvin K K Lakkaraju1, Camille Mary, Anne Scherrer
1Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Geneva, Switzerland.
Cell
|May 6, 2008
概括
信号识别粒子 (SRP) 延迟对于有效地将蛋白质向内质网膜 (ER) 至关重要. 这种机制通过协调翻译与蛋白质转位来防止细胞缺陷,确保适当的蛋白质折叠和功能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 信号识别粒子 (SRP) 途径将蛋白质定位到内质网膜 (ER).
- 已知SRP在延缓新生的多链延长中的作用,但其体内重要性尚不清楚.
- 由于SRP受体 (SR) 的可用性有限,细胞翻译速率可能与有效的蛋白质转移不相容.
研究的目的:
- 研究哺乳动物细胞中SRP介导的延长停止的功能意义.
- 确定SRP的延迟功能是否对有效的蛋白质向和细胞平衡至关重要.
- 阐明翻译速率,SRP功能和蛋白质转位之间的关系.
主要方法:
- 哺乳动物细胞中SRP14的耗尽,随后补充野生型和突变型SRP14,缺乏延长停止功能.
- 分析蛋白质转位效率,分泌缺陷,膜蛋白水平和细胞生长率.
- 操纵细胞蛋白质合成速率和SRP受体 (SR) 表达水平.
主要成果:
- 没有SRP14的哺乳动物细胞表达非捕获突变体,表现出低效的蛋白质向ER.
- 这些细胞显示出蛋白质分泌的显著缺陷,内源性膜蛋白质的枯竭,以及细胞生长的减少.
- 降低蛋白质合成速率或增加SR表达率挽救了有害影响,突出了协调翻译和转位的重要性.
- 通过SRP介导的延迟确保新生的链在SR依赖的时间窗口内保持转移能力.
结论:
- 通过SRP介导的延长停止对于有效的蛋白质转移到ER in vivo至关重要.
- 这种延迟机制对于维持细胞平衡,适当的蛋白质分泌和细胞生长至关重要.
- SRP延迟功能作为协调蛋白质合成与ER转位能力的调节机制,可能会影响基于SRP信号序列亲缘关系的特定蛋白质的向.
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