合作选择未折叠的蛋白质反应以引起嗅觉受体反
Ryan P Dalton1, David B Lyons, Stavros Lomvardas
1Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA.
Cell
|October 15, 2013
概括
嗅觉受体 (OR) 蛋白质触发了展开的蛋白质反应 (UPR),以保持神经元的身份. 这个过程涉及ATF5的选择性翻译,导致Adcy3表达和永久的OR选择.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 嗅觉受体 (OR) 在嗅觉感官神经元 (OSN) 中的表达涉及选择成千上万的OR基因之一.
- 为了保持这种特定的OR转录选择,反机制至关重要.
- 目前尚不清楚OSN如何检测OR并向细胞核发出这种选择的信号.
研究的目的:
- 阐明OR蛋白质向核产生反信号的机制.
- 研究未折叠蛋白反应 (UPR) 在维持OR表达和神经元身份方面的作用.
主要方法:
- 研究了未折叠蛋白反应 (UPR) 在OR表达中的作用.
- 研究了OSN中涉及Perk,eif2α,ATF5和Adcy3的信号通路.
- 提出并支持OR反信号的两步模型.
主要成果:
- OR蛋白激活了UPR,诱导了ep2α的Perk介导酸化.
- 这导致激活转录因子5 (ATF5) 的选择性翻译.
- ATF5驱动Adcy3转录,这随后缓解了UPR并稳定了OR表达.
结论:
- 在神经元身份和细胞命运承诺中,UPR起着至关重要的作用.
- 一个两步反模型解释了OR表达是如何维持的:最初的UPR激活,然后是Adcy3介导的减压.
- 这种机制确保了选择的OR基因在OSN中的持久性.
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