异常相位分离驱动膜性器官重塑和瘤发生
Xinyu Wang1, Amin Jiang1, Quan Meng2
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Molecular cell
|April 24, 2025
概括
融合蛋白的液态相分离 (LLPS) 驱动活细胞中的膜重塑. 这一过程重编程细胞,有助于低度纤维化瘤的发展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- 膜重塑对于细胞功能至关重要.
- 液-液相分离 (LLPS) 在人工系统中驱动膜重塑.
- 在活细胞膜重塑和疾病中LLPS的作用尚不清楚.
研究的目的:
- 在活细胞中研究LLPS介导的膜重塑.
- 确定内在无序区域 (IDR) 丰富的整体跨膜融合蛋白 (MFP) 在细胞过程中的作用.
- 为了阐明FUS-CREB3L2在低度纤维肌肉瘤 (LGFMS) 发育中的机制.
主要方法:
- 超高分辨率的长时间成像对内分泌网膜 (ER) 重塑.
- 分析FUS-CREB3L2积累及其对ER压力的影响.
- 对X盒结合蛋白1 (XBP1) 路径激活的研究.
- 研究从ER膜到核的信号传导.
主要成果:
- 富含IDR的MFP诱导活细胞中细胞器的新膜重塑.
- FUS-CREB3L2积累导致ER压力并劫持XBP1通路.
- FUS-CREB3L2异常的LLPS效应从ER膜转导到核中.
- FUS-CREB3L2激活了LGFMS特异性基因,将细胞重新编程成LGFMS类状态.
结论:
- 多型细胞的LLPS驱动活细胞中显著的膜重塑.
- FUS-CREB3L2通过异常的LLPS重编程细胞功能,作为LGFMS的驱动器.
- 这项研究揭示了LLPS介导的膜重塑在癌症发展中的新机制.
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