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运动神经元轴突终末中核糖体与内质网的动态重塑

Dynamic remodeling of ribosomes and endoplasmic reticulum in axon terminals of motoneurons.

作者信息

Deng Chunchu, Moradi Mehri, Reinhard Sebastian, Ji Changhe, Jablonka Sibylle, Hennlein Luisa, Lüningschrör Patrick, Doose Sören, Sauer Markus, Sendtner Michael

机构信息

Institute of Clinical Neurobiology, University Hospital Würzburg, 97078 Würzburg, Germany.

Department of Biotechnology and Biophysics, Biocenter, Julius-Maximilians-University Würzburg, 97074 Würzburg, Germany.

出版信息

J Cell Sci. 2021 Nov 15;134(22). doi: 10.1242/jcs.258785. Epub 2021 Nov 16.

Abstract

In neurons, the endoplasmic reticulum (ER) forms a highly dynamic network that enters axons and presynaptic terminals and plays a central role in Ca2+ homeostasis and synapse maintenance; however, the underlying mechanisms involved in regulation of its dynamic remodeling as well as its function in axon development and presynaptic differentiation remain elusive. Here, we used high-resolution microscopy and live-cell imaging to investigate rapid movements of the ER and ribosomes in axons of cultured motoneurons after stimulation with brain-derived neurotrophic factor. Our results indicate that the ER extends into axonal growth cone filopodia, where its integrity and dynamic remodeling are regulated mainly by actin and the actin-based motor protein myosin VI (encoded by Myo6). Additionally, we found that in axonal growth cones, ribosomes assemble into 80S subunits within seconds and associate with the ER in response to extracellular stimuli, which describes a novel function of axonal ER in dynamic regulation of local translation. This article has an associated First Person interview with Chunchu Deng, joint first author of the paper.

摘要

在神经元中,内质网(ER)形成一个高度动态的网络,该网络进入轴突和突触前终末,并在钙离子稳态和突触维持中发挥核心作用;然而,其动态重塑的调控机制以及在轴突发育和突触前分化中的功能仍不清楚。在这里,我们使用高分辨率显微镜和活细胞成像技术,研究了脑源性神经营养因子刺激后培养的运动神经元轴突中内质网和核糖体的快速移动。我们的结果表明,内质网延伸至轴突生长锥丝状伪足中,其完整性和动态重塑主要受肌动蛋白和基于肌动蛋白的运动蛋白肌球蛋白VI(由Myo6编码)调控。此外,我们发现,在轴突生长锥中,核糖体在数秒内组装成80S亚基,并响应细胞外刺激与内质网结合,这揭示了轴突内质网在局部翻译动态调控中的新功能。本文还有对该论文的共同第一作者邓春初进行的相关第一人称访谈。

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