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通过RILP-RAB7A的晚期内体运输促进了树树木化

Chan Choo Yap^1,2,3,4, Laura Digilio^1,2,3,4, Lloyd P McMahon^1,2,3,4

¹Department of Cell Biology, University of Virginia, 1340 Jefferson Park Avenue, Pinn Hall 3226, Charlottesville, VA 22908, USA.

bioRxiv : the preprint server for biology

|December 15, 2025

概括

树的生长需要RAB7A/RILP依赖的晚期内体 (LEs) 运输,即使降解不受影响. 这项研究揭示了LE运动在神经元发育中的新角色.

科学领域:

细胞生物学细胞生物学
神经科学是一个神经科学.
分子生物学分子生物学

背景情况:

晚期内分泌体 (LEs) 逆向运输到 soma 对于 lysosomal 融合和降解至关重要.
树突性LE运动性和体性降解取决于RAB7A和dynein.
RAB7A和dynein通过RILP连接在一起,RAB7A的效应器也与HOPS复合体相互作用.

研究的目的:

调查RAB7A-RILP相互作用在神经元内体运输,降解和树形态学中的作用.
根据非神经元细胞研究,测试神经元内基因组运动和降解取决于RILP的假设.

主要方法:

功能分离的RAB7A突变体 (RAB7A-L8A) 的表达,该突变体不能在培养的老鼠和小鼠海马神经元中结合RILP.
在表达RAB7A-L8A的神经元中分析了晚期内体运动,溶酶体融合,载荷降解和树树木化.

主要成果:

内生RILP作为RAB7A依赖的dynein适配器,用于树突中的LE运动,促进内生体载体的形成.
通过RAB7A-L8A表达来抑制LE运输,导致退化载荷从树突中受到损害的清除.
溶酶体融合和体性降解仍然正常,表明这些过程不需要RAB7A-RILP相互作用.
尽管正常降解,但RAB7A-L8A表达神经元的树木化受损,将形态缺陷与降解阻塞分开.

结论:

神经元状体的生长和维护取决于RAB7A/RILP介导的晚期内体运输.
RAB7A-RILP相互作用对于树突中的LE运动性和货物清除是必不可少的,但对于 lysosomal 融合或体质降解不是.
树形态缺陷可以从降解阻塞中分离出来,突出显示了LE运输在神经元发育中的独特作用.

关键词:

在 RAB7A 效应器中使用 RAB7A 效应器.在RILP中,RILP是指RILP.树突运输是一种树突运输.这就是dyneinin的意思.晚期内分泌体内分泌体的时间.神经元神经元的神经元

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