同时结合引导线索NET1和RGM阻断细胞外NEO1信号
Ross A Robinson1, Samuel C Griffiths1, Lieke L van de Haar2
1Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Cell
|March 19, 2021
概括
新生素 (NEO1) 通过形成三元复合体来整合来自Netrin-1 (NET1) 和排斥指导分子 (RGM) 的对立信号. 这种超级组合使下游信号沉默, 防止细胞生长圆崩并调节神经元迁移.
科学领域:
- 分子生物学
- 神经科学
- 细胞生物学
背景情况:
- 细胞表面受体在迁移和分化等关键过程中整合各种细胞外信号.
- 新生素 (NEO1) 具有双重功能,通过Netrin-1 (NET1) 进行吸引,并通过排斥指导分子 (RGM) 连接物进行排斥.
研究的目的:
- 阐明信号整合的机制,当NEO1同时与具有相反功能的联体结合时.
- 确定NEO1如何调和吸引力和排斥力的结构基础.
主要方法:
- 用X射线结晶学来确定NEO1-NET1-RGM复合物的结构.
- 生物化学测试以评估下游的信号.
- 基于细胞的测试以评估生长缩和神经元迁移.
主要成果:
- 一个由NEO1,NET1和RGM组成的三元复合体,在细胞膜上形成一个"三元体的三元体"超级组合.
- 这种超级组合抑制了RGMA- NEO1介导的生长缩和RGMA/ NET1- NEO1介导的神经元迁移.
- 超级组件可以防止信号竞争复合体的形成和NEO1ectodomain集群.
结论:
- 同时与单个受体结合并不总是导致竞争性信号传递.
- 一个更高阶的超复杂构造可以导致对立的功能输出相互沉默.
- 这种机制提供了关于细胞如何整合复杂的细胞外线索以获得精确的细胞反应的见解.
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