Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA.
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Cell Rep. 2023 Nov 28;42(11):113327. doi: 10.1016/j.celrep.2023.113327. Epub 2023 Oct 30.
Circuit refinement involves the formation of new presynaptic boutons as others are dismantled. Nascent presynaptic sites can incorporate material from recently eliminated synapses, but the recycling mechanisms remain elusive. In early-stage C. elegans larvae, the presynaptic boutons of GABAergic DD neurons are removed and new outputs established at alternative sites. Here, we show that developmentally regulated expression of the epithelial Na channel (ENaC) UNC-8 in remodeling DD neurons promotes a Ca and actin-dependent mechanism, involving activity-dependent bulk endocytosis (ADBE), that recycles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. In contrast, we find that an ADBE-like mechanism results in the distal recycling of synaptic material from old to new synapses. Thus, our findings suggest that a native mechanism (ADBE) can be repurposed to dismantle presynaptic terminals for reassembly at new, distant locations.
回路细化涉及新的突触前末梢的形成，而其他末梢则被拆除。新形成的突触前部位可以整合来自最近消除的突触的物质，但回收机制仍然难以捉摸。在早期的秀丽隐杆线虫幼虫中， GABAergic DD 神经元的突触前末梢被去除，并在替代部位建立新的输出。在这里，我们表明，上皮钠通道（ENaC）UNC-8 在重塑 DD 神经元中的发育调控表达促进了一种 Ca 和肌动蛋白依赖性机制，涉及活性依赖性体內内吞（ADBE），该机制回收突触前物质，用于在新形成的 DD 突触处重新组装。ADBE 通常在高度活跃的神经元中发挥作用，以加速突触小泡的局部回收。相比之下，我们发现一种类似于 ADBE 的机制导致从旧突触到新突触的远端回收突触物质。因此，我们的研究结果表明，一种天然机制（ADBE）可以被重新用于拆卸突触前末梢，以便在新的、遥远的位置重新组装。
