ABSTRACT

It is increasingly recognized that local protein synthesis (LPS) contributes to fundamental aspects of axon biology, in both developing and mature neurons. Mutations in RNA-binding proteins (RBPs), as central players in LPS, and other proteins affecting RNA localization and translation are associated with a range of neurological disorders, suggesting disruption of LPS may be of pathological significance. In this review, we substantiate this hypothesis by examining the link between LPS and key axonal processes, and the implicated pathophysiological consequences of dysregulated LPS. First, we describe how the length and autonomy of axons result in an exceptional reliance on LPS. We next discuss the roles of LPS in maintaining axonal structural and functional polarity and axonal trafficking. We then consider how LPS facilitates the establishment of neuronal connectivity through regulation of axonal branching and pruning, how it mediates axonal survival into adulthood and its involvement in neuronal stress responses.

摘要

人们越来越认识到局部蛋白质合成 (LPS) 在发育和成熟神经元中对轴突生物学的基本方面有贡献。作为 LPS 核心参与者的 RNA 结合蛋白 (RBP) 和其他影响 RNA 定位和翻译的蛋白质的突变与一系列神经系统疾病有关，这表明 LPS 的破坏可能具有病理学意义。在这篇综述中，我们通过检查 LPS 和关键轴突过程之间的联系以及 LPS 失调的相关病理生理后果来证实这一假设。首先，我们描述了轴突的长度和自主性如何导致对 LPS 的异常依赖。我们接下来讨论 LPS 在维持轴突结构和功能极性以及轴突运输方面的作用。