Science—中间能神经元重磅突破：ErbB4-Tsc2信号通路调控PV+中间神经元兴奋性突触的形成

中文摘要

神经元使用局部蛋白质合成来支持其形态复杂性，而这需要完成跨多个亚细胞区室的独立控制，直到实现单个突触水平的控制。科学家确定了一条信号通路，该通路调节小鼠大脑皮层中表达小清蛋白（PV+）的中间神经元上形成兴奋性突触所需蛋白质的局部合成。该过程涉及Erb-B2受体酪氨酸激酶4（ErbB4）对TSC亚基2（Tsc2）的调节，这使得大脑能够以细胞类型特异性和突触类型特异性的方式对信使RNA｛mRNA｝翻译进行局部控制。核糖体相关mRNA谱揭示了ErbB4信号下游突触蛋白的分子程序，而ErbB4信号是PV+中间神经元上形成兴奋性突触所必需的。因此，特定的连接使用局部蛋白质合成来控制神经系统中突触的形成。

英文摘要

Neurons use local protein synthesis to support their morphological complexity, which requires independent control across multiple subcellular compartments up to the level of individual synapses. We identify a signaling pathway that regulates the local synthesis of proteins required to form excitatory synapses on parvalbumin-expressing (PV+) interneurons in the mouse cerebral cortex. This process involves regulation of the TSC subunit 2 (Tsc2) by the Erb-B2 receptor tyrosine kinase 4 (ErbB4), which enables local control of messenger RNA {mRNA} translation in a cell type-specific and synapse type-specific manner. Ribosome-associated mRNA profiling reveals a molecular program of synaptic proteins downstream of ErbB4 signaling required to form excitatory inputs on PV+ interneurons. Thus, specific connections use local protein synthesis to control synapse formation in the nervous system.

参考文献：Cortical wiring by synapse type-specific control of local protein synthesis. Science. 2022 Nov 25;378(6622):eabm7466. doi: 10.1126/science.abm7466. Epub 2022 Nov 25.

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