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脑源性神经营养因子减少 eEF2 磷酸化并增强背根神经节神经元生长锥中新型蛋白质的合成。

BDNF Reduces eEF2 Phosphorylation and Enhances Novel Protein Synthesis in the Growth Cones of Dorsal Root Ganglia Neurons.

机构信息

Department of Anatomy and Physiological Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.

出版信息

Neurochem Res. 2018 Jun;43(6):1242-1249. doi: 10.1007/s11064-018-2541-8. Epub 2018 May 7.

Abstract

The local translation, which is regulated by extracellular stimuli such as guidance molecules, in growth cones of neurons provides a molecular mechanism for axonal development. In this study, we performed immunocytochemistry together with atomic force microscopy to investigate the localization of ribosomal proteins in the growth cones of rat dorsal root ganglion (DRG) neurons. The immunoreactivity of ribosomal protein P0/1/2 and S6, and novel protein synthesis were observed in the central, sterically bulky region of growth cones. Brain derived neurotrophic factor (BDNF) reduced the eEF2 phosphorylation, indicating its activation, and enhanced protein synthesis within 30 min. The effects of BDNF were completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). These results indicated that BDNF rapidly activates translation and enhances novel protein synthesis in growth cones of DRG though the mTOR signaling.

摘要

神经元生长锥中的局部翻译受细胞外刺激(如导向分子)的调节,为轴突发育提供了分子机制。在这项研究中,我们通过免疫细胞化学和原子力显微镜观察了核糖体蛋白在大鼠背根神经节(DRG)神经元生长锥中的定位。核糖体蛋白 P0/1/2 和 S6 的免疫反应性以及新蛋白质的合成在生长锥的中央、空间庞大的区域观察到。脑源性神经营养因子(BDNF)降低了 eEF2 的磷酸化,表明其被激活,并在 30 分钟内增强了蛋白质的合成。BDNF 的作用被 rapamycin(一种哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂)完全抑制。这些结果表明,BDNF 通过 mTOR 信号通路迅速激活翻译并增强 DRG 生长锥中的新蛋白质合成。

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