胆固醇调节胰岛素诱导的mTORC1信号传递
Kolaparamba V Navyasree1,2, Shikha T Ramesh1,2, Perunthottathu K Umasankar1
1Intracellular Trafficking Laboratory, Transdisciplinary Biology Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala 695014, India.
Journal of cell science
|November 3, 2023
概括
胆固醇对于胰岛素刺激的机械点拉巴胺素复合物-1 (mTORC1) 信号传递至关重要,对于细胞生长至关重要. 这项研究揭示了胆固醇.
科学领域:
- 细胞信号传递和新陈代谢
- 增长调节的分子机制.
背景情况:
- 拉巴胺素复合体-1 (mTORC1) 信号传递的胰岛素刺激的机械标对哺乳动物细胞生长至关重要.
- 控制胰岛素诱导的mTORC1激活的精确调节因素仍然不完全理解.
研究的目的:
- 阐明胆固醇在调节胰岛素刺激的mTORC1信号传递中的作用.
- 研究胆固醇如何影响mTORC1的局部化和激活.
- 探索胆固醇在饥饿期间mTORC1重激活中的作用及其对史密斯-莱姆利-奥皮茨综合征 (SLOS) 的影响.
主要方法:
- 细胞胆固醇的消耗和补充.
- 分析mTORC1对溶解体的招募和TSC复合体解离.
- 研究胆固醇与mTORC1重新激活的自的相互作用.
- 在SLOS纤维细胞和HeLa-SLOS细胞中评估胰岛素-mTORC1信号.
主要成果:
- 胰岛素诱导的mTORC1信号在缺乏胆固醇的细胞中受损,并在胆固醇补充后恢复.
- 胆固醇有助于mTORC1向 lysosomes的招募,促进完整的激活,而不会改变TSC复杂的动态.
- 胆固醇与自合作,使mTORC1在饥饿下重新激活,挽救胰岛素反应.
- 缺乏胆固醇生物合成的SLOS细胞表现出缺陷的胰岛素-mTORC1信号,由胆固醇补充或激活Rag GTPase来挽救.
结论:
- 胆固醇是胰岛素刺激的mTORC1信号的关键调节者,对于细胞生长至关重要.
- 胆固醇通过 lysosomal 招募协调 mTORC1 激活的空间和时间控制.
- 胆固醇生物合成的缺陷导致mTORC1信号受损,突出显示胆固醇在生长调节和疾病中的重要性.
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