Dastidar Sudhriti Ghosh, Nair Deepak
Centre for Neuroscience, Indian Institute of Science, Bengaluru, India.
Front Mol Neurosci. 2022 Feb 23;15:823135. doi: 10.3389/fnmol.2022.823135. eCollection 2022.
Continued mRNA translation and protein production are critical for various neuronal functions. In addition to the precise sorting of proteins from cell soma to distant locations, protein synthesis allows a dynamic remodeling of the local proteome in a spatially variable manner. This spatial heterogeneity of protein synthesis is shaped by several factors such as injury, guidance cues, developmental cues, neuromodulators, and synaptic activity. In matured neurons, thousands of synapses are non-uniformly distributed throughout the dendritic arbor. At any given moment, the activity of individual synapses varies over a wide range, giving rise to the variability in protein synthesis. While past studies have primarily focused on the translation factors or the identity of translated mRNAs to explain the source of this variation, the role of ribosomes in this regard continues to remain unclear. Here, we discuss how several stochastic mechanisms modulate ribosomal functions, contributing to the variability in neuronal protein expression. Also, we point out several underexplored factors such as local ion concentration, availability of tRNA or ATP during translation, and molecular composition and organization of a compartment that can influence protein synthesis and its variability in neurons.
持续的mRNA翻译和蛋白质合成对于各种神经元功能至关重要。除了将蛋白质从细胞体精确分选到远处之外，蛋白质合成还允许以空间可变的方式对局部蛋白质组进行动态重塑。蛋白质合成的这种空间异质性受到多种因素的影响，如损伤、导向线索、发育线索、神经调质和突触活动。在成熟的神经元中，数千个突触非均匀地分布在整个树突分支上。在任何给定时刻，单个突触的活动在很大范围内变化，导致蛋白质合成的变异性。虽然过去的研究主要集中在翻译因子或翻译后的mRNA的身份来解释这种变化的来源，但核糖体在这方面的作用仍然不清楚。在这里，我们讨论了几种随机机制如何调节核糖体功能，从而导致神经元蛋白质表达的变异性。此外，我们指出了几个尚未充分探索的因素，如局部离子浓度、翻译过程中tRNA或ATP的可用性，以及能够影响神经元中蛋白质合成及其变异性的隔室的分子组成和组织。
