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重复的ER-内体接触促进内体转位和神经元外生长
Camilla Raiborg1, Eva M Wenzel1, Nina M Pedersen1
11] Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, Norway [2] Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
Nature
|April 10, 2015
概括
普罗鲁丁形成了内质网膜 (ER) - 末端内体 (LE) 接触点,促进了素-1的转移. 这一过程将LEs驱动到细胞外围,促进突起和神经元外生长.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 细胞内膜网膜 (ER) 和内体通过接触点连接,这对细胞过程至关重要.
- 精确的机制和ER-内体接触点的功能尚未完全理解.
- 众所周知,一种ER蛋白质Protrudin可以影响细胞突起和神经元外生.
研究的目的:
- 为了阐明protrudin在ER-endosome接触点中的作用.
- 研究ER-内体接触如何调节内体贩运和细胞形态.
- 为了确定参与protrudin介导的ER-endosome相互作用的分子参与者.
主要方法:
- 使用了人类和老鼠细胞系.
- 使用共免疫沉和近距离结合试验研究了蛋白质相互作用.
- 使用活细胞成像来追踪内体运动和ER-内体接触.
- 利用siRNA和CRISPR/Cas9来耗尽或淘汰关键蛋白质.
主要成果:
- 普罗鲁丁通过识别RAB7和酸酸 (PtdIns(3) P) 来形成与晚期内体 (LEs) 的接触点.
- 这些接触点促进了LEs上的kinesin-1运动蛋白从protrudin转移到FYCO1.
- 重复的ER-LE接触促进了基因素-1驱动的LE转移到细胞外围,导致等离子体膜融合,突起和神经元外生长.
结论:
- 通过protrudin介导的ER-LE接触点作为基因素-1加载到LEs的平台.
- 由ER接触提供燃料的基因素-1-依赖的LE运输对于突起和神经元外生是必不可少的.
- 这项研究揭示了一种新的机制,将ER-内分体接触动态与神经元发育和细胞形态联系起来.
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