Active zone compaction in presynaptic homeostatic potentiation

Active zone compaction in presynaptic homeostatic potentiation
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突触前稳态增强中的活动区压缩

DOI:
10.1101/802843
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发表时间:
2020
期刊:
bioRxiv
影响因子:
--
通讯作者:
Paul MM
Paul MM
中科院分区:
--
文献类型:
--
作者:
Mrestani A;Kollmannsberger P;Pauli M;Repp F;Kittel RJ;Eilers J;Doose S;Sauer M;Sirén A-L;Heckmann M;Paul MM

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神经递质的释放是由稳态可塑性稳定的。突触前稳态增强(PHP)在从分钟到终生适应的时间尺度上起作用,可能涉及突触前活动区(AZs)的重组。在果蝇的黑腹神经肌肉接头,早期的工作将AZ的扩大归因于加入更多的BruchPilot(BRP)支架蛋白在PHP中的作用。我们使用定位显微镜(直接随机光学重建显微镜[dSTORM])和基于层次密度的带噪声应用程序的空间聚集(HDBSCAN)来研究突触中尺度上的AZ可塑性。我们发现,在急性和慢性遗传诱导的PHP中,单个AZ紧凑,但AZ蛋白的拷贝数没有变化。紧凑甚至发生在BRP亚簇和Rab3相互作用分子(RIM)结合蛋白(RBP)亚簇水平上,这些亚簇向AZ中心移动。此外,相关的共聚焦和dSTORM成像揭示了如前面所暗示的,PHP中的AZ压缩如何转化为AZ面积和BRP蛋白含量的明显增加。
Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic homeostatic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). AtDrosophila melanogasterneuromuscular junctions, earlier work ascribed AZ enlargement by incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction microscopy [dSTORM]) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) to study AZ plasticity during PHP at the synaptic mesoscale. We find compaction of individual AZs in acute philanthotoxin-induced and chronic genetically induced PHP but unchanged copy numbers of AZ proteins. Compaction even occurs at the level of Brp subclusters, which move toward AZ centers, and in Rab3 interacting molecule (RIM)-binding protein (RBP) subclusters. Furthermore, correlative confocal and dSTORM imaging reveals how AZ compaction in PHP translates into apparent increases in AZ area and Brp protein content, as implied earlier.
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