The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane.
The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane.
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DOI：
10.1042/bcj20160580
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
K. Obara;A. Kihara
中科院分区：
文献类型：
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作者：
K. Obara;A. Kihara
酵母细胞通过传感器蛋白 Rim21 感知质膜 (PM) 脂质不对称性和外部碱化的变化，该蛋白在 Rim101 通路中发挥作用。 Rim101 信号传导在 PM 处通过 Rim101 信号传导复合物的募集而启动。 PM 与皮质内质网 (ER) 物理结合，形成 ER-PM 接触位点，在此发生多种信号传导事件、脂质交换和离子传输。在本研究中，我们研究了 ER-PM 接触位点和 Rim101 信号传导位点之间的空间关系。 Rim101 信号传导主要在 PM 中的 ER-PM 接触位点之外进行，并且不需要完整的 ER-PM 接触来激活。相反，Rim101 通路是通过 ER-PM 接触位点破坏而组成型激活的，已知这会导致 ER 应激。衣霉素治疗诱导的 ER 应激激活了 Rim101 通路。此外，通过删除 RIM21，细胞对没有 ER-PM 接触的衣霉素的敏感性显着提高。这些结果表明，Rim101 途径通过补偿 ER 应激引起的 PM 脂质不对称性的变化，对于适应 ER 应激非常重要。
Yeast cells sense alterations in the plasma membrane (PM) lipid asymmetry and external alkalization by the sensor protein Rim21, which functions in the Rim101 pathway. Rim101 signaling is initiated at the PM by the recruitment of the Rim101 signaling complex. The PM physically associates with the cortical endoplasmic reticulum (ER) to form ER-PM contact sites, where several signaling events, lipid exchange, and ion transport take place. In the present study, we investigated the spatial relationship between ER-PM contact sites and the sites of Rim101 signaling. Rim101 signaling mostly proceeds outside ER-PM contact sites in the PM and did not require intact ER-PM contact for its activation. Rather, the Rim101 pathway was constitutively activated by ER-PM contact site disruption, which is known to cause ER stress. ER stress induced by tunicamycin treatment activated the Rim101 pathway. Furthermore, the sensitivity of cells to tunicamycin without ER-PM contact was considerably elevated by the deletion of RIM21. These results suggest that the Rim101 pathway is important for the adaptation to ER stress by compensating for alterations in PM lipid asymmetry induced by ER stress.