Postsynaptic Syntaxin 4 negatively regulates the efficiency of neurotransmitter release

Signaling from the postsynaptic compartment regulates multiple aspects of synaptic development and function. Syntaxin 4 (Syx4) is a plasma membrane t-SNARE that promotes the growth and plasticity of <i>Drosophila</i> neuromuscular junctions (NMJs) by regulating the localization of key synaptic proteins in the postsynaptic compartment. Here, we describe electrophysiological analyses and report that loss of <i>Syx4</i> leads to enhanced neurotransmitter release, despite a decrease in the number of active zones. We describe a requirement for postsynaptic <i>Syx4</i> in regulating several presynaptic parameters, including Ca²⁺ cooperativity and the abundance of the presynaptic calcium channel Cacophony (Cac) at active zones. These findings indicate Syx4 negatively regulates presynaptic neurotransmitter release through a retrograde signaling mechanism from the postsynaptic compartment.

突触后区室（postsynaptic compartment）的信号通路调控突触发育与功能的多个维度。Syntaxin 4（Syx4）是一类质膜t-SNARE蛋白，可通过调控突触后区室内关键突触蛋白的定位，促进果蝇（Drosophila）神经肌肉接头（neuromuscular junctions, NMJs）的生长与突触可塑性。本研究开展电生理分析后发现：尽管活性区（active zones）的数量有所减少，Syx4的缺失会导致神经递质释放量显著增强。本研究明确了突触后Syx4在调控多项突触前参数中的必要作用，包括钙离子协同性（Ca²+ cooperativity）以及活性区突触前钙离子通道Cacophony（Cac）的蛋白丰度。上述研究结果证实，Syx4可通过源自突触后区室的逆行信号机制（retrograde signaling mechanism），负向调控突触前神经递质的释放。