NG2 cells as receivers and transducers of neuronal network signals via locally translated mRNA

NG2胶质细胞独特地与灰质和白质中的神经元形成突触，在那里它们代表突触后间隔。神经元通过调节定位于突触的RNA的翻译来响应突触信号。这允许对远离细胞体的信号做出快速且可控的反应。以类似的方式，我们假设NG2胶质细胞在本地翻译特定定位于突起和突触的mRNAs。我们已经确定了一系列定位于NG2细胞过程中的mRNAs，并确定了本地翻译的候选基因。两个特别有趣的蛋白质是已知与活性启动子结合的变异组蛋白，以及转录因子Orig2。我们已经证明，在谷氨酸的刺激下，分离的NG2细胞可以诱导H3.3a定位的RNA翻译成蛋白质。在这个项目中，我们将进一步研究影响这种局部翻译的刺激(电生理学和生理学)，并调节蛋白质到其作用部位的运输(例如进入细胞核)。因此，我们打算揭示NG2胶质细胞如何通过局部翻译mRNA来响应网络活动，以及这是如何塑造它们的分化和功能特性的。

NG2 glia uniquely form synapses with neurons in both grey and white matter where they represent a postsynaptic compartment. Neurons respond to synaptic signals by regulating translation of synaptically localized RNAs. This allows a fast and controlled response to a signal perceived far away from the cell body. In a similar fashion we hypothesise that NG2 glia locally translate mRNAs specifically localized in processes and synapses. We have identified a range of mRNAs that are localized in NG2 cell processes and have identified candidates for local translation. Two particularly interesting proteins are a variant histone known to bind to active promoters, and the transcription factor Olig2. We have shown that stimulation of isolated NG2+ cells in culture with glutamate induces translation of H3.3a localized RNA into protein. In this project we will further investigate the stimuli (electrophysiological and physiological) that impinge on such local translation and regulate transport of the proteins to their sites of action (e.g. into the cell nucleus). We thus intend to unravel how NG2 glia respond to network activity via local translation of mRNA and how this shapes their differentiation and functional properties.