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核糖体相关囊泡促进活性依赖的局部翻译。

Ribosome-Associated Vesicles promote activity-dependent local translation.

作者信息

Martin-Solana Eva, Carter Stephen D, Donahue Eric K F, Ning Jiying, Glausier Jill R, Preisegger Matias A, Eisenman Leanna, Joseph Paul N, Bouchet-Marquis Cedric, Wu Ken, Mobini Catherina L, Frantz Amber N, Puig Stephanie, Hampton Cheri M, Kabbani Nadine, Jensen Grant J, Watkins Simon C, Deisseroth Karl, Fenno Lief E, Gold Michael S, Wills Zachary P, Burkewitz Kristopher, Das Sulagna, Freyberg Zachary

机构信息

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.

出版信息

bioRxiv. 2024 Jun 10:2024.06.07.598007. doi: 10.1101/2024.06.07.598007.

Abstract

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes. Stimulation via chemically-induced long-term potentiation causes RAV accumulation in distal sites to drive local translation. We also demonstrate activity-driven changes in RAV generation and dynamics , identifying tubular ER shaping proteins in RAV biogenesis. Together, our work identifies a mechanism for ribosomal delivery to distal sites in neurons to promote activity-dependent local translation.

摘要

轴突和树突中的局部蛋白质合成是突触可塑性的基础。然而,远端神经元突起中蛋白质合成机制的组成以及其活性驱动的向局部翻译位点的部署机制仍不清楚。在这里,我们采用冷冻电子断层扫描、体积电子显微镜和活细胞成像技术,将核糖体相关囊泡(RAV)鉴定为将核糖体转运到远端突起的动态平台。通过化学诱导的长时程增强进行刺激会导致RAV在远端位点积累,从而驱动局部翻译。我们还证明了RAV生成和动力学的活性驱动变化,确定了RAV生物发生中的管状内质网塑形蛋白。总之,我们的工作确定了一种将核糖体递送至神经元远端位点以促进活性依赖的局部翻译的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7e/11185778/0833086d6715/nihpp-2024.06.07.598007v2-f0001.jpg

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