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突触后突触核蛋白介导内源性大麻素信号
作者:小柯机器人 发布时间:2023/6/2 11:24:48

美国斯坦福大学Jun B. Ding和Thomas C. Südhof共同合作,近期取得重要工作进展。他们研究发现突触后突触核蛋白介导内源性大麻素信号。相关研究成果2023年5月29日在线发表于《自然—神经科学》杂志上。

据介绍,内源性大麻素是整个神经系统突触传递最强大的调节器之一,但人们对内源性大麻肽从突触后区室的释放知之甚少。

研究人员报告了一个意想不到的发现,内源性大麻素的释放需要突触核蛋白,这是帕金森病的关键因素。研究人员发现内源性大麻素通过突触核蛋白依赖性和SNARE依赖性机制在突触后释放。突触核蛋白缺失阻断内源性大麻素依赖性突触可塑性,这种阻断被野生型的突触后表达所逆转,而不是突变型的α-突触核蛋白。对内源性大麻素信号传导的全细胞记录和直接光学监测表明,突触核蛋白缺失特异性阻断内源性大麻毒素的释放。

鉴于突触前突触核蛋白在调节囊泡生命周期中的作用,研究人员假设内源性大麻素是通过膜相互作用机制释放的。与这一假设一致的是,破伤风毒素轻链的突触后表达也阻断了内源性大麻素依赖性信号传导。

总之,内源性大麻素通过突触核蛋白依赖性机制释放的意外发现与突触核蛋白在膜运输中的一般功能一致,并为神经元如何释放内源性大麻素以诱导突触可塑性的长期谜题增进了理解。

附:英文原文

Title: Postsynaptic synucleins mediate endocannabinoid signaling

Author: Albarran, Eddy, Sun, Yue, Liu, Yu, Raju, Karthik, Dong, Ao, Li, Yulong, Wang, Sui, Sdhof, Thomas C., Ding, Jun B.

Issue&Volume: 2023-05-29

Abstract: Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, and yet little is understood about the release of endocannabinoids from postsynaptic compartments. Here we report an unexpected finding that endocannabinoid release requires synucleins, key contributors to Parkinson’s disease. We show that endocannabinoids are released postsynaptically by a synuclein-dependent and SNARE-dependent mechanism. Specifically, we found that synuclein deletion blocks endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wild-type but not of mutant α-synuclein. Whole-cell recordings and direct optical monitoring of endocannabinoid signaling suggest that the synuclein deletion specifically blocks endocannabinoid release. Given the presynaptic role of synucleins in regulating vesicle lifecycle, we hypothesize that endocannabinoids are released via a membrane interaction mechanism. Consistent with this hypothesis, postsynaptic expression of tetanus toxin light chain, which cleaves synaptobrevin SNAREs, also blocks endocannabinoid-dependent signaling. The unexpected finding that endocannabinoids are released via a synuclein-dependent mechanism is consistent with a general function of synucleins in membrane trafficking and adds a piece to the longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.

DOI: 10.1038/s41593-023-01345-0

Source: https://www.nature.com/articles/s41593-023-01345-0

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex