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研究揭示海马GABAA受体中相组织结构
2020-11-05 12:51

中国科学技术大学毕国强、刘北明以及美国加州大学洛杉矶分校周正洪合作取得最新进展。他们揭示了海马抑制性突触中A型GABA受体(GABAARs)的中相组织结构。这一研究成果于2020年10月2日发表在《自然-神经科学》杂志上。

在这项研究中,使用无模板的过采样子亚断层图分类来分析海马突触的冷冻电子断层图。他们在抑制性突触中鉴定了GABAARs,并确定了它们在19-Å分辨率下的原位结构。这些受体是按层次组织的:从距离有11 nm但相对角度可变优选受体的GABAAR超复合物,到具有降低的Voronoi熵的半序二维受体网络,再到具有清晰相边界的中相组装。

这些组装可能通过突触后支架蛋白和受体之间的相互作用形成,并与假定的突触前囊泡释放位点对齐。这种中间相的自组织可能使突触达到“Goldilocks”状态,从而在稳定性和灵活性之间取得平衡,并使信息处理具有可塑性。

据了解,脑中的信息处理取决于突触后密度内神经递质受体和支架蛋白的专门组织。但是,这些分子在原位的组织方式仍是未知的。

附:英文原文

Title: Mesophasic organization of GABA A receptors in hippocampal inhibitory synapses

Author: Yun-Tao Liu, Chang-Lu Tao, Xiaokang Zhang, Wenjun Xia, Dong-Qing Shi, Lei Qi, Cheng Xu, Rong Sun, Xiao-Wei Li, Pak-Ming Lau, Z. Hong Zhou, Guo-Qiang Bi

Issue&Volume: 2020-11-02

Abstract: Information processing in the brain depends on specialized organization of neurotransmitter receptors and scaffolding proteins within the postsynaptic density. However, how these molecules are organized in situ remains largely unknown. In this study, template-free classification of oversampled sub-tomograms was used to analyze cryo-electron tomograms of hippocampal synapses. We identified type-A GABA receptors (GABAARs) in inhibitory synapses and determined their in situ structure at 19- resolution. These receptors are organized hierarchically: from GABAAR super-complexes with a preferred inter-receptor distance of 11nm but variable relative angles, through semi-ordered, two-dimensional receptor networks with reduced Voronoi entropy, to mesophasic assembly with a sharp phase boundary. These assemblies likely form via interactions among postsynaptic scaffolding proteins and receptors and align with putative presynaptic vesicle release sites. Such mesophasic self-organization might allow synapses to achieve a ‘Goldilocks’ state, striking a balance between stability and flexibility and enabling plasticity in information processing.

DOI: 10.1038/s41593-020-00729-w

Source: https://www.nature.com/articles/s41593-020-00729-w

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


本期文章:《自然—神经科学》:Online/在线发表

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