Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany.
FEBS Lett. 2018 Nov;592(21):3516-3531. doi: 10.1002/1873-3468.13188. Epub 2018 Jul 31.
Synaptic transmission relies on the rapid fusion of neurotransmitter-containing synaptic vesicles (SVs), which happens in response to action potential (AP)-induced Ca influx at active zones (AZs). A highly conserved molecular machinery cooperates at SV-release sites to mediate SV plasma membrane attachment and maturation, Ca sensing, and membrane fusion. Despite this high degree of conservation, synapses - even within the same organism, organ or neuron - are highly diverse regarding the probability of APs to trigger SV fusion. Additionally, repetitive activation can lead to either strengthening or weakening of transmission. In this review, we discuss mechanisms controlling release probability and this short-term plasticity. We argue that an important layer of control is exerted by evolutionarily conserved AZ scaffolding proteins, which determine the coupling distance between SV fusion sites and voltage-gated Ca channels (VGCC) and, thereby, shape synapse-specific input/output behaviors. We propose that AZ-scaffold modifications may occur to adapt the coupling distance during synapse maturation and plastic regulation of synapse strength.
突触传递依赖于神经递质囊泡（SVs）的快速融合，这是响应动作电位（AP）诱导的活性区（AZ）内 Ca 流入而发生的。高度保守的分子机制在 SV 释放位点协同作用，介导 SV 质膜附着和成熟、Ca 感应和膜融合。尽管具有高度的保守性，但突触——即使在同一生物体、器官或神经元内——在 AP 触发 SV 融合的概率方面也存在很大的差异。此外，重复激活会导致传递的增强或减弱。在这篇综述中，我们讨论了控制释放概率和这种短期可塑性的机制。我们认为，进化上保守的 AZ 支架蛋白施加了一个重要的控制层，决定了 SV 融合位点和电压门控 Ca 通道（VGCC）之间的耦合距离，从而形成了特定于突触的输入/输出行为。我们提出，AZ 支架的修饰可能会发生，以适应突触成熟过程中的耦合距离和突触强度的可塑性调节。
