聚类原卡德林神经自我识别复合体的可视化
Julia Brasch1,2,3, Kerry M Goodman1,3, Alex J Noble2
1Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY, USA.
Nature
|April 12, 2019
概括
神经元的自我识别依赖于形成拉链状结构的聚类原始素. 这些分子组合调解神经元避开,对神经系统的正常发育和功能至关重要.
科学领域:
- 神经科学
- 分子生物学
- 结构生物学
背景情况:
- 神经细胞自我识别和避免对于神经系统的发展至关重要,指导树树木化并防止自我连接.
- 集群原素 (PCDH) 及其多种异型为个体神经元提供独特的身份,调解自我识别.
- 之前的研究单独描述了protocadherin的cis和trans相互作用,但全长的ectodomain结构及其在神经元表面自我识别中的作用仍然未知.
研究的目的:
- 在自我识别复合体中确定全长集群的原始干细胞体的分子排列.
- 阐明protocadherins如何调解神经元自我识别和避免的结构基础.
主要方法:
- 使用X射线结晶学来确定聚类原cadherin γB4的结构.
- 使用冷电子断层扫描可视化了脂质体上聚合的原卡德林 γB6 ectodomains 的组合.
主要成果:
- 聚类原cadherin γB4 的晶体结构显示了由交替的 cis 和 trans 相互作用形成的类似拉链的格子.
- 低温电子断层扫描表明,集群的原卡德林 γB6 ectodomains 在膜接触部位自发组装成线性阵列.
- 这些线性组合形成平行阵列,在膜之间创建更大的二维结构,与晶体结构一致.
结论:
- 通过聚类原素形成有序的线性组合是神经元自我识别和避免的关键初步步骤.
- 这些发现支持了以protocadherin为媒介的自我识别的异型不匹配链终结模型.
- 这项研究提供了关于protocadherins如何建立神经元边界和确保神经系统正确连接的结构见解.
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