Nup358通过调节mTORC2/Akt/GSK3β信号传递来限制ER-线粒体的连接
Misha Kalarikkal1, Rimpi Saikia1, Lizanne Oliveira1
1National Centre for Cell Science, S.P. Pune University Campus, Pune, Maharashtra, 411007, India.
EMBO reports
|July 18, 2024
概括
像Nup358这样的取消层 (AL) 蛋白调节内网膜-线粒体接触部位 (ERMCSs). 通过调节mTORC2/Akt/GSK3β通路,Nup358的耗尽增强了ERMCS,揭示了一个新的控制机制.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 器官生物学 有机生物学
背景情况:
- 细胞内网膜-线粒体接触部位 (ERMCS) 对于细胞功能,如平衡和新陈代谢至关重要.
- 虽然mTORC2/Akt稳定了ERMCS,GSK3β减少了它们的连接性,但确切的监管机制尚不清楚.
- 无效片 (AL),含有核素的ER子域,以前没有与ERMCS法规联系在一起.
研究的目的:
- 为了研究废除的片 (AL) 和它们的居住核波林在调节ER-线粒体接触部位 (ERMCSs) 中的作用.
- 阐明核波林控制ERMCS的分子机制,重点关注mTORC2/Akt/GSK3β信号轴.
主要方法:
- 使用siRNA.358 (一种AL核) 和Rictor (一种mTORC2子单元) 的耗尽.
- 分析ER-线粒体连接和mTORC2/Akt/GSK3β信号通路的激活.
- 对Nup358片段的表达,以评估其在VAPB-PTPIP51复杂相互作用中的功能作用.
主要成果:
- 耗尽Nup358导致ERMCSs增加,增强mTORC2 / Akt激活,以及GSK3β抑制.
- 里克托衰减或外源GSK3β表达逆转了Nup358缺乏细胞中的ERMCS表型.
- Nup358与VAPB-PTPIP51复合体直接相互作用,限制了mTORC2 / Akt信号和ERMCS连接.
结论:
- 在ERMCS中局部化取消层状膜的Nup358,充当ER-线粒体连接的新型调节者.
- Nup358通过调节mTORC2/Akt/GSK3β信号轴来控制ERMCS.
- 这项研究揭示了一种以前未知的ERMCS调节机制,涉及核素.
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