A trans-synaptic nanocolumn aligns neurotransmitter release to receptors.
A trans-synaptic nanocolumn aligns neurotransmitter release to receptors.
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DOI：
10.1038/nature19058
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发表时间：
2016-08-11
期刊：
影响因子：
64.8
通讯作者：
Blanpied, Thomas A.
中科院分区：
文献类型：
--
作者：
Tang, Ai-Hui;Chen, Haiwen;Li, Tuo P.;Metzbower, Sarah R.;MacGillavry, Harold D.;Blanpied, Thomas A.
突触传递由微妙的突触下分子结构维持，即使突触结构的轻微改变也会在经验依赖性可塑性和病理性疾病期间驱动功能变化。这种结构的关键是突触前囊泡融合位点的分布如何对应于突触后密度中受体的位置。然而，尽管这种空间关系调节突触强度的认识由来已久，但由于光学显微镜的分辨率有限，尚未对其进行精确描述。使用本地化显微镜，我们在这里报告，介导囊泡启动和融合的关键蛋白质相互共同丰富的突触前活动区的纳米尺度的子区域内。通过开发一种新的方法来映射单个突触内的囊泡融合位置，我们发现，动作电位诱发的融合是由这种蛋白质梯度引导的，并且优先发生在活动区内RIM局部密度较高的受限区域。这些突触前RIM纳米簇与集中的突触后受体和支架蛋白紧密对齐，表明跨突触分子“纳米柱”。因此，我们建议，活性区的纳米架构指导动作电位诱发囊泡融合优先发生在直接反对突触后受体支架合奏的网站。值得注意的是，NMDA受体激活触发了不同阶段的可塑性，其中突触后重组其次是跨突触纳米级的重新排列。因此，这种结构表明了CNS突触维持和调节突触效率的简单组织原理。
Synaptic transmission is maintained by a delicate, subsynaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorder. Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, despite long recognition that this spatial relationship modulates synaptic strength, it has not been precisely described, due in part to the limited resolution of light microscopy. Using localization microscopy, we report here that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometer-scaled subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses, we found that action potential evoked fusion was guided by this protein gradient and occurred preferentially in confined areas with higher local density of RIM within the active zones. These presynaptic RIM nanoclusters closely aligned with concentrated postsynaptic receptors and scaffolding proteins, suggesting a transsynaptic molecular “nanocolumn.” Thus, we propose that the nanoarchitecture of the active zone directs action potential evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor-scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by transsynaptic nanoscale realignment. This architecture thus suggests a simple organizational principle of CNS synapses to maintain and modulate synaptic efficiency.
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影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
16.2
作者：
Frank, Thomas;Rutherford, Mark A.;Strenzke, Nicola;Neef, Andreas;Pangrsic, Tina;Khimich, Darina;Fetjova, Anna;Gundelfinger, Eckart D.;Liberman, M. Charles;Harke, Benjamin;Bryan, Keith E.;Lee, Amy;Egner, Alexander;Riedel, Dietmar;Moser, Tobias
通讯作者：
Moser, Tobias
影响因子：
16.2
作者：
Kim, Sung Hyun;Ryan, Timothy A.
通讯作者：
Ryan, Timothy A.
影响因子：
16.2
作者：
Frost, Nicholas A.;Shroff, Hari;Kong, Huihui;Betzig, Eric;Blanpied, Thomas A.
通讯作者：
Blanpied, Thomas A.
DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF