Department of Biochemistry, University of Oxford, Oxford, UK.
Medical Research Council Lab for Molecular Cell Biology, University College London, London, UK.
J Cell Biol. 2020 Mar 2;219(3). doi: 10.1083/jcb.201903135.
Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.
记忆和学习涉及蛋白质的活性驱动表达和新突触处细胞骨架的重组，这需要远距离从相应细胞核对局部 mRNA 进行转录后调控。在突触形成早期表达的关键因子是 Msp300/Nesprin-1，它围绕新突触组织肌动蛋白丝。Msp300 在突触可塑性过程中的表达如何受到调控还知之甚少。在这里，我们表明，果蝇幼虫肌神经接点的突触后隔室中 Msp300 的活性依赖性积累受保守 RNA 结合蛋白 Syncrip/hnRNP Q 调控。Syncrip（Syp）与 msp300 转录本结合，对可塑性至关重要。单分子成像显示 msp300 在体内与 Syp 相关，并形成富含核糖体的颗粒，其中包含翻译因子 eIF4E。神经活动增加改变了 Syp 的动力学以及突触处 msp300：Syp：eIF4E RNP 颗粒的数量，表明这些颗粒促进了翻译。这些结果表明 Syp 是一个重要的早期活性依赖性可塑性基因调节剂，与人类共济失调密切相关。
