研究人员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。这一过程涉及Erb-B2受体酪氨酸激酶4（ErbB4）对TSC亚单位2（TSC2）的调控，这使得信使RNA（mRNA）的翻译以细胞类型特异性和突触类型特异性的方式得到局部控制。核糖体相关的mRNA分析揭示了ErbB4信号下游的突触蛋白的分子程序，该程序需要在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的蛋白质合成来控制神经系统中突触的形成。
据悉，神经元利用局部蛋白质的合成来支持其形态的复杂性，这需要在多个亚细胞区间的独立控制，直至单个突触的水平。
附：英文原文
Title: Cortical wiring by synapse type–specific control of local protein synthesis
Author: Clémence Bernard, David Exposito-Alonso, Martijn Selten, Stella Sanalidou, Alicia Hanusz-Godoy, Alfonso Aguilera, Fursham Hamid, Fazal Oozeer, Patricia Maeso, Leanne Allison, Matthew Russell, Roland A. Fleck, Beatriz Rico, Oscar Marín
Issue&Volume: 2022-11-25
Abstract: 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.
DOI: abm7466
Source: https://www.science.org/doi/10.1126/science.abm7466