需要mTORC1激活剂SLC38A9从溶酶体中排出必需的氨基酸并使用蛋白质作为营养物质
Gregory A Wyant1, Monther Abu-Remaileh1, Rachel L Wolfson2
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
氨酸通过 lysosomal 蛋白 SLC38A9 激活 mTORC1 途径,该蛋白也调节了细胞生长的必需氨基酸的释放.
科学领域:
- 细胞生物学
- 生物化学
- 分子生物学
背景情况:
- 拉巴胺复合物1 (mTORC1) 激酶的机械性标是细胞生长的关键调节剂,对营养的可用性有反应.
- 溶酶体氨基酸的传感和运输对于细胞平衡至关重要,但根本的机制仍然不完全理解.
研究的目的:
- 阐明SLC38A9在氨基酸感应和mTORC1激活中的功能.
- 研究SLC38A9在氨基酸运输和细胞代谢中的作用.
主要方法:
- 验证SLC38A9作为mTORC1的阿金因传感器.
- 分析从溶酶体中SLC38A9介导的必需氨基酸的运输.
- 评估SLC38A9在胰腺瘤形成中的作用.
主要成果:
- SLC38A9充当氨酸传感器,将氨酸的可用性与mTORC1的激活联系起来.
- SLC38A9促进了包括白在内的必需氨基酸从溶解体的流出.
- 通过SLC38A9从溶酶体释放的白蛋白是mTORC1激活所需的.
- 胰腺癌细胞依赖于SLC38A9进行瘤生长,利用巨细胞细胞的营养.
结论:
- 通过SLC38A9,氨酸作为一种溶解体信使来调节mTORC1的活动.
- SLC38A9对于氨基酸平衡和由营养驱动的细胞生长至关重要.
- 针对SLC38A9可能为依赖营养清理的癌症提供治疗策略.
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