通过ERp44和PDIA6在压力下对抗细胞内网膜保留的对抗调节
Olaya Yassin1, Bellam Praveen2, Odai Darawshi1
1Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
The Biochemical journal
|December 2, 2024
概括
选择性ER保留 (sERr) 糖蛋白,包括氨酸激酶受体是可逆的. 从sERr恢复取决于IRE1和PDIA6,而ERp44和PTEN影响其动力学.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞内膜网膜 (ER) 的压力通过翻译调节影响蛋白质合成,特别是通过eIF2α激酶PERK.
- 在ER应激过程中抑制PERK会导致特定糖蛋白的选择性ER保留 (sERr),特别是氨酸激酶受体 (RTK),形成大型二硫化物结合复合体.
- 蛋白二硫化异构酶ERp44促进sERr并增加这些复合物的大小.
研究的目的:
- 研究选择性ER保留 (sERr) 的可逆性和调节恢复的分子机制.
- 阐明未折叠蛋白质响应传感器IRE1和蛋白质二硫化物异构酶PDIA6在sERr动态中的作用.
- 探索RTK信号传递之间的相互作用,包括瘤抑制剂PTEN和sERr.
主要方法:
- 脉冲追踪分析以追踪ER应激和恢复期间的蛋白质贩运和复合体形成.
- 研究ERp44和PDIA6对sERr和恢复动力学的相互作用和功能影响.
- 使用ERp44,PDIA6和PTEN的遗传删除来评估它们对sERr和蛋白质合成的影响.
主要成果:
- 在消除ER压力条件后,选择性ER保留 (sERr) 是可逆的.
- 从sERr中恢复被展开的蛋白质响应传感器IRE1加速,并受到PDIA6和ERp44的影响,它们具有相反的效果.
- 删除ERp44加速恢复,而删除PDIA6则减缓恢复,对整体蛋白质合成的影响最小. 删除PTEN有助于sERr的形成和恢复.
结论:
- 选择性ER保留 (sERr) 是一个动态和可逆的过程. 涉及IRE1和PDIA6的适应机制抵消了sERr.
- ERp44和PDIA6在SERr之后的蛋白质贩运恢复的监管中发挥着关键的,对立的作用.
- 由PTEN调节的RTK信号与sERr及其恢复的动力学之间存在一个反循环.
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