Cortical wiring by synapse type-specific control of local protein synthesis
Cortical wiring by synapse type-specific control of local protein synthesis
复制标题
DOI：
10.1126/science.abm7466
复制
发表时间：
2022-11-25
期刊：
影响因子：
56.9
通讯作者：
Marin, Oscar
中科院分区：
文献类型：
--
作者：
Bernard, Clemence;Exposito-Alonso, David;Marin, Oscar
神经元使用局部蛋白质合成来支持其形态复杂性，这需要跨多个亚细胞区室的独立控制，直到单个突触的水平。我们确定了一个信号通路，调节局部蛋白质的合成所需的小清蛋白表达（PV+）的中间神经元在小鼠大脑皮层形成兴奋性突触。该过程涉及Erb-B2受体酪氨酸激酶4（ErbB 4）对TSC亚基2（Tsc 2）的调节，其能够以细胞类型特异性和突触类型特异性方式局部控制信使RNA {mRNA}翻译。核糖体相关的mRNA分析揭示了ErbB 4信号下游突触蛋白的分子程序，其需要在PV+中间神经元上形成兴奋性输入。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。
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.