小柯机器人

突触囊泡的快速补给需要突触结合蛋白-3
2022-10-23 14:46

近日,美国俄勒冈健康与科学大学Skyler L. Jackman及其研究小组发现,突触囊泡的快速补给需要突触结合蛋白-3。相关论文于2022年10月19日在线发表在《自然》杂志上。

研究人员将突触结合蛋白-3(Syt3)确定为突触前高亲和力Ca2+传感器,它驱动囊泡补充和短期突触可塑性。Syt3敲除小鼠的突触表现出更强的短期抑制,而且从抑制中恢复的速度较慢,对突触前残留的Ca2+不敏感。在持续的神经元发射过程中,Syt3加速了囊泡的补充,并增加了可随时释放的囊泡池的大小。SYT3还在低释放概率的条件下介导短期促进作用,并与另一个高亲和力的突触结合蛋白SYT7一起促进突触增强。生物物理模型预测,SYT3通过促进松散对接的囊泡向紧密对接的引物状态过渡,来介导补充和促进作用。

这些结果揭示了突触前SYT3在维持可靠的高频突触传递中的关键作用。此外,多种形式的短期可塑性可能汇聚在一个可逆的、依赖Ca2+的囊泡对接机制上。

据介绍,持续的神经元活动需要突触囊泡的快速补给以维持可靠的突触传递。这种囊泡的补充是由一个尚未确定的高亲和力Ca2+传感器发出的亚微摩尔突触前Ca2+信号加速的。

附:英文原文

Title: Fast resupply of synaptic vesicles requires synaptotagmin-3

Author: Weingarten, Dennis J., Shrestha, Amita, Juda-Nelson, Kessa, Kissiwaa, Sarah A., Spruston, Evan, Jackman, Skyler L.

Issue&Volume: 2022-10-19

Abstract: Sustained neuronal activity demands a rapid resupply of synaptic vesicles to maintain reliable synaptic transmission. Such vesicle replenishment is accelerated by submicromolar presynaptic Ca2+ signals by an as-yet unidentified high-affinity Ca2+ sensor1,2. Here we identify synaptotagmin-3 (SYT3)3,4 as that presynaptic high-affinity Ca2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity. Synapses in Syt3 knockout mice exhibited enhanced short-term depression, and recovery from depression was slower and insensitive to presynaptic residual Ca2+. During sustained neuronal firing, SYT3 accelerated vesicle replenishment and increased the size of the readily releasable pool. SYT3 also mediated short-term facilitation under conditions of low release probability and promoted synaptic enhancement together with another high-affinity synaptotagmin, SYT7 (ref. 5). Biophysical modelling predicted that SYT3 mediates both replenishment and facilitation by promoting the transition of loosely docked vesicles to tightly docked, primed states. Our results reveal a crucial role for presynaptic SYT3 in the maintenance of reliable high-frequency synaptic transmission. Moreover, multiple forms of short-term plasticity may converge on a mechanism of reversible, Ca2+-dependent vesicle docking.

DOI: 10.1038/s41586-022-05337-1

Source: https://www.nature.com/articles/s41586-022-05337-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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