mTORC1信号传递和内酶体中活性蛋白结构的相互依赖
Amulya Priya1, Sandra Antoine-Bally1, Anne-Sophie Macé2
1Institut Curie, CNRS UMR144, PSL Research University, Research Center, Actin and Membrane Dynamics Laboratory, 26 rue d'Ulm, Paris 75248 Cedex 05, France.
Science advances
|September 13, 2023
概括
拉巴胺素复合体1 (mTORC1) 的机械性标与内溶性体活性相互作用. 这项研究揭示了actin对于mTORC1信号传递和endolysosomes上的营养感应至关重要.
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:
- 拉巴胺素复合体1 (mTORC1) 的机械标是细胞生长和新陈代谢的关键调节者,由营养的可用性激活.
- mTORC1的激活发生在内解体表面,在那里它感知氨基酸.
- 内分泌体微域是由分支的活性蛋白网络形成的,由WASH和Arp2/3复合体产生的.
研究的目的:
- 为了研究mTORC1信号传递和内溶性体活性之间的关系.
- 为了识别将mTORC1组件与内解酶体活性蛋白网络联系起来的蛋白质.
主要方法:
- 蛋白质组分析以确定RAGC的相互作用体,这是mTORC1.1的溶酶体结合体.
- 扰乱RAGC功能和内溶体动态动态动态 (使用WASH和Arp2/3沉默).
- 药理上抑制了动素聚合的过程.
- 显微镜评估mTORC1组件和活性的局部位置.
主要成果:
- 发现mTORC1的组件与内解体性actin微域非常接近.
- 蛋白质学确定了actin丝封闭蛋白和调节器作为RAGC相互作用体.
- RAGC 功能干扰改变了内溶体的行为体大小,表明RAGC 调节了行为体封闭.
- 抑制actin聚合或破坏内溶体actin受损的mTORC1活动.
- 动氨酸对于RAGC和mTOR与内溶酶体的正确关联至关重要.
结论:
- 这项研究揭示了actin动力学和mTORC1在内分泌体上的信号传递之间的新型相互作用.
- 在内解体系统上的动蛋白对于适当的mTORC1定位和营养感应功能至关重要.
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