The exocytosis regulator complexin controls spontaneous synaptic vesicle release in a CAPS-dependent manner at C. elegans excitatory synapses.

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Tác giả: Lili Chen, Xuhui Chen, Chun Hin Chow, Yixiang Deng, Shangbang Gao, Randa Higazy, Mengjia Huang, Cong Ma, Neeraja Ramakrishnan, Shuzo Sugita, Sheng Wang, Ya Wang, Cuntai Zhang, Yu Zhang

Ngôn ngữ: eng

Ký hiệu phân loại: 305.568 +Alienated and excluded classes

Thông tin xuất bản: United States : PLoS biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 192718

The balance between synaptic excitation and inhibition (E/I) is essential for coordinating motor behavior, yet the differential roles of exocytosis regulators in this balance are less understood. In this study, we investigated the roles of 2 conserved exocytosis regulators, complexin/CPX-1 and CAPS/UNC-31, in excitatory versus inhibitory synapses at Caenorhabditis elegans neuromuscular junctions. cpx-1 null mutants exhibited a marked increase in spontaneous release specifically at excitatory synapses, alongside an unequal reduction in excitatory and inhibitory evoked release. A clamping-specific knockin mutant, cpx-1(Δ12), which preserved evoked release, also showed a biased enhancement in excitatory spontaneous release. Conversely, the unc-31 null mutation, while maintaining normal spontaneous release, displayed a more pronounced reduction in evoked release at excitatory synapses. Notably, we found that CPX-1's clamping function is dependent on UNC-31 and is sensitive to external Ca2+. Pull-down experiments confirmed that CAPS/UNC-31 does not directly interact with complexin, implying an indirect regulatory mechanism. Moreover, complexin regulates activity-dependent synaptic plasticity, which is also UNC-31 dependent. The unexpected role of CAPS/UNC-31 in the absence of CPX-1 clamping function may underpin the synaptic E/I balance and coordinated behavioral outputs in different species.
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