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小鼠皮层抑制性突触中的超快内吞作用。

Ultrafast endocytosis in mouse cortical inhibitory synapses.

作者信息

Eddings Chelsy R, Watanabe Shigeki

机构信息

Department of Cell Biology, The Johns Hopkins University, Baltimore MD, 21205, USA.

Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University, Baltimore MD, 21205, USA.

出版信息

bioRxiv. 2025 Jun 8:2025.06.06.658279. doi: 10.1101/2025.06.06.658279.

DOI:10.1101/2025.06.06.658279
PMID:40501796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12157488/
Abstract

Neural circuitry depends on excitatory and inhibitory regulation of activity to yield functional outputs. However, examinations of synaptic vesicle recycling have focused heavily on excitatory synapses, leaving many questions unanswered for inhibitory synapse dynamics. Here we show that both excitatory and inhibitory cortical synapses contain depots of a protein essential for ultrafast endocytosis, Dynamin 1xA, at a region immediately next to the active zone where ultrafast endocytosis takes place. Using zap-and-freeze time-resolved electron microscopy in mouse acute cortical slices, we observe uncoated pits reminiscent of ultrafast endocytic intermediates appearing post-stimulus at putative inhibitory synapses. These findings suggest that excitatory and inhibitory synapses may perform similar modes of endocytosis.

摘要

神经回路依赖于对活动的兴奋性和抑制性调节来产生功能性输出。然而,对突触小泡循环的研究主要集中在兴奋性突触上,关于抑制性突触动力学仍有许多问题未得到解答。在这里,我们表明,兴奋性和抑制性皮质突触在紧邻发生超快内吞作用的活性区的区域都含有一种对超快内吞作用至关重要的蛋白质——发动蛋白1xA的储存库。利用小鼠急性皮质切片中的电刺激和冷冻时间分辨电子显微镜,我们在假定的抑制性突触中观察到了刺激后出现的类似超快内吞中间体的无包被小窝。这些发现表明,兴奋性和抑制性突触可能执行相似的内吞模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/0c058da9f90d/nihpp-2025.06.06.658279v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/b07a0a385857/nihpp-2025.06.06.658279v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/1f641c030d04/nihpp-2025.06.06.658279v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/51896d8801a5/nihpp-2025.06.06.658279v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/0c058da9f90d/nihpp-2025.06.06.658279v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/b07a0a385857/nihpp-2025.06.06.658279v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/1f641c030d04/nihpp-2025.06.06.658279v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/51896d8801a5/nihpp-2025.06.06.658279v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d26/12157488/0c058da9f90d/nihpp-2025.06.06.658279v1-f0004.jpg

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本文引用的文献

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Understanding GABAergic synapse diversity and its implications for GABAergic pharmacotherapy.理解GABA能突触多样性及其对GABA能药物治疗的意义。
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GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.死后背外侧前额叶皮质中的γ-氨基丁酸能功能障碍:对精神分裂症和情感障碍认知缺陷的影响
Front Cell Neurosci. 2024 Sep 24;18:1440834. doi: 10.3389/fncel.2024.1440834. eCollection 2024.
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Cereb Cortex. 2024 Aug 1;34(8). doi: 10.1093/cercor/bhae312.
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Interactions Involving Glycine and Other Amino Acid Neurotransmitters: Focus on Transporter-Mediated Regulation of Release and Glycine-Glutamate Crosstalk.涉及甘氨酸和其他氨基酸神经递质的相互作用:聚焦于转运体介导的释放调节及甘氨酸-谷氨酸相互作用
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Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.动力蛋白 1xA 通过其拼接的长 C 末端与内收蛋白 A1 相互作用,实现超快内吞作用。
EMBO J. 2024 Aug;43(16):3327-3357. doi: 10.1038/s44318-024-00145-x. Epub 2024 Jun 21.
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Increased number of excitatory synapsis and decreased number of inhibitory synapsis in the prefrontal cortex in autism.自闭症患者前额叶皮质中兴奋性突触数量增加,抑制性突触数量减少。
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