Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific.

Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific.
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DOI:
10.1038/s41467-022-28504-4
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发表时间:
2022-02-17
影响因子:
16.6
通讯作者:
Dalva MB
Dalva MB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hruska M;Cain RE;Dalva MB

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异源四聚体谷氨酸受体对于脊柱突触的发育、功能和可塑性是必不可少的,但它们如何组织以实现这一点尚不清楚。在这里,我们表明,含有特定亚基的谷氨酸受体的纳米级组织定义不同的突触下功能。含有GluA 2或GluN 1亚基的谷氨酸受体建立相对于突触结合蛋白-1阳性突触前释放位点精确定位的纳米模块元件,所述突触前释放位点随脊柱大小缩放。含有GluA 1或GluN 2B的谷氨酸受体指定表现出灵活性的特征:含有GluA 1亚基的AMPAR在较大的棘中发现,而含有GluN 2B亚基的NMDAR在最小的棘中富集,两者都不遵循严格的模块化组织。鉴于不同类别的谷氨酸受体的精确定位与包括细胞死亡和突触可塑性在内的多种事件有关,这种出乎意料的强大突触纳米结构提供了一种弹性系统,其中纳米定位的谷氨酸受体异四聚体定义了单个棘突触的特定突触下区域。谷氨酸受体包括两个专性亚基和两个赋予特定四聚体不同性质和功能的亚基,其也定位于不同的突触棘。在这里,作者使用模拟发射耗尽纳米显微镜(STED)来提供对谷氨酸受体类型的空间组织的详细见解。
Heterotetrameric glutamate receptors are essential for the development, function, and plasticity of spine synapses but how they are organized to achieve this is not known. Here we show that the nanoscale organization of glutamate receptors containing specific subunits define distinct subsynaptic features. Glutamate receptors containing GluA2 or GluN1 subunits establish nanomodular elements precisely positioned relative to Synaptotagmin-1 positive presynaptic release sites that scale with spine size. Glutamate receptors containing GluA1 or GluN2B specify features that exhibit flexibility: GluA1-subunit containing AMPARs are found in larger spines, while GluN2B-subunit containing NMDARs are enriched in the smallest spines with neither following a strict modular organization. Given that the precise positioning of distinct classes of glutamate receptors is linked to diverse events including cell death and synaptic plasticity, this unexpectedly robust synaptic nanoarchitecture provides a resilient system, where nanopositioned glutamate receptor heterotetramers define specific subsynaptic regions of individual spine synapses. Glutamate receptors comprise two obligate subunits and two subunits that confer distinct properties and functions to the specific tetramers, which also localize to distinct synaptic spines. Here, the authors use STimulated Emission Depletion nanoscopy (STED) to provide detailed insights into the spatial organization of glutamate receptor types.
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