Vollum Institute, Oregon Health & Science University, Portland, OR, USA.
Vollum Institute, Oregon Health & Science University, Portland, OR, USA.
Cell Rep. 2024 Aug 27;43(8):114595. doi: 10.1016/j.celrep.2024.114595. Epub 2024 Aug 6.
Neurotransmitter release consists of rapid synchronous release followed by longer-lasting asynchronous release (AR). Although the presynaptic proteins that trigger synchronous release are well understood, the mechanisms for AR remain unclear. AR is sustained by low concentrations of intracellular Ca and Sr, suggesting the involvement of sensors with high affinities for both ions. Synaptotagmin 7 (SYT7) partly mediates AR, but substantial AR persists in the absence of SYT7. The closely related SYT3 binds Ca and Sr with high affinity, making it a promising candidate to mediate AR. Here, we use knockout mice to study the contribution of SYT3 and SYT7 to AR at cerebellar and hippocampal synapses. AR is dramatically reduced when both isoforms are absent, which alters the number and timing of postsynaptic action potentials. Our results confirm the long-standing prediction that SYT3 mediates AR and show that SYT3 and SYT7 act as dominant mechanisms for AR at three central synapses.
神经递质释放包括快速同步释放和持续时间更长的异步释放 (AR)。虽然触发同步释放的突触前蛋白已经得到很好的理解，但 AR 的机制仍不清楚。AR 由低浓度的细胞内 Ca 和 Sr 维持，这表明涉及对两种离子具有高亲和力的传感器。突触结合蛋白 7 (SYT7) 部分介导 AR，但在没有 SYT7 的情况下仍存在大量 AR。与其密切相关的 SYT3 与 Ca 和 Sr 具有高亲和力，使其成为介导 AR 的有希望的候选者。在这里，我们使用基因敲除小鼠来研究 SYT3 和 SYT7 在小脑和海马突触中对 AR 的贡献。当两种异构体都不存在时，AR 会显著减少，这会改变突触后动作电位的数量和时间。我们的结果证实了 SYT3 介导 AR 的长期预测，并表明 SYT3 和 SYT7 是三个中枢突触 AR 的主要机制。
