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

NG2胶质细胞与灰色和白色物质中的神经元形成突触，它们代表突触后隔室。神经元通过调节突触定位RNA的翻译来响应突触信号。这允许对远离细胞体感知的信号做出快速和受控的响应。以类似的方式，我们假设NG2神经胶质细胞在局部翻译特定定位于过程和突触中的mRNA。我们已经鉴定了一系列定位于NG2细胞过程中的mRNA，并鉴定了局部翻译的候选者。两种特别有趣的蛋白质是已知与活性启动子结合的变体组蛋白和转录因子Olig2。我们已经表明，用谷氨酸刺激培养物中分离的NG2+细胞诱导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（电生理和生理），并调节蛋白质运输到其作用位点（例如进入细胞核）。因此，我们打算解开NG2神经胶质细胞如何通过mRNA的局部翻译来响应网络活动，以及这如何塑造它们的分化和功能特性。

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.