Department of Pathology and Anatomical Sciences, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8519, Japan.
Department of Brain Tumor Biology, Brain Research Institute, Niigata University, Niigata, 951-8510, Japan.
Neurochem Res. 2024 Oct;49(10):2774-2784. doi: 10.1007/s11064-024-04195-9. Epub 2024 Jul 8.
Local translation in growth cones plays a critical role in responses to extracellular stimuli, such as axon guidance cues. We previously showed that brain-derived neurotrophic factor activates translation and enhances novel protein synthesis through the activation of mammalian target of rapamycin complex 1 signaling in growth cones of dorsal root ganglion neurons. In this study, we focused on 40S ribosomal protein S6 (RPS6), 60S ribosomal protein P0/1/2 (RPP0/1/2), and actin filaments to determine how localization of ribosomal proteins changes with overall protein synthesis induced by neurotrophins. Our quantitative analysis using immunocytochemistry and super-resolution microscopy indicated that RPS6, RPP0/1/2, and actin tend to colocalize in the absence of stimulation, and that these ribosomal proteins tend to dissociate from actin and associate with each other when local protein synthesis is enhanced. We propose that this is because stimulation causes ribosomal subunits to associate with each other to form actively translating ribosomes (polysomes). This study further clarifies the role of cytoskeletal components in local translation in growth cones.
在生长锥中进行的局部翻译在响应细胞外刺激(如轴突导向线索)中起着关键作用。我们之前曾表明,脑源性神经营养因子通过激活生长锥中的哺乳动物雷帕霉素靶蛋白复合物 1 信号通路来激活翻译并增强新蛋白质的合成。在这项研究中,我们专注于 40S 核糖体蛋白 S6(RPS6)、60S 核糖体蛋白 P0/1/2(RPP0/1/2)和肌动蛋白丝,以确定核糖体蛋白的定位如何随神经营养因子诱导的整体蛋白质合成而变化。我们使用免疫细胞化学和超分辨率显微镜进行的定量分析表明,在没有刺激的情况下,RPS6、RPP0/1/2 和肌动蛋白倾向于共定位,并且当局部蛋白质合成增强时,这些核糖体蛋白倾向于从肌动蛋白解离并彼此结合。我们提出,这是因为刺激导致核糖体亚基彼此结合形成活跃翻译的核糖体(多核糖体)。这项研究进一步阐明了细胞骨架成分在生长锥中局部翻译中的作用。