ABSTRACT Bafilomycin A1, a vacuolar H+-ATPase inhibitor, and botulinum toxin B and tetanus toxin, both vesicle fusion inhibitors, are widely known exocytosis blockers that have been used to inhibit the presynaptic release of neurotransmitters. However, protein trafficking mechanisms, such as the insertion of postsynaptic receptors and astrocytic glutamate-releasing channels into the plasma membrane, also require exocytosis. In our previous study, exocytosis inhibitors reduced the surface expression of astrocytic glutamate-releasing channels. Here, we further investigated whether exocytosis inhibitors influence the surface expression of postsynaptic receptors. Using pH-sensitive superecliptic pHluorin (SEP)-tagged postsynaptic glutamate receptors, including GluA1, GluA2, GluN1, and GluN2A, we found that bafilomycin A1, botulinum toxin B, and/or tetanus toxin reduce the SEP fluorescence of SEP-GluA1, SEP-GluA2, SEP-GluN1, and SEP-GluN2A. These findings indicate that presynaptic vesicle exocytosis inhibitors also affect the postsynaptic trafficking machinery for surface expression. Finally, this study provides profound insights assembling presynaptic, postsynaptic and astrocytic viewpoints into the interpretation of the data obtained using these synaptic vesicle exocytosis inhibitors.

中文翻译：

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突触小泡胞吐抑制剂降低突触后谷氨酸受体的表面表达

摘要 Bafilomycin A1 是一种液泡 H+-ATP 酶抑制剂，肉毒杆菌毒素 B 和破伤风毒素都是囊泡融合抑制剂，是众所周知的胞吐作用阻滞剂，已被用于抑制神经递质的突触前释放。然而，蛋白质运输机制，如突触后受体和星形胶质细胞谷氨酸释放通道插入质膜，也需要胞吐作用。在我们之前的研究中，胞吐作用抑制剂降低了星形胶质细胞谷氨酸释放通道的表面表达。在这里，我们进一步研究了胞吐作用抑制剂是否影响突触后受体的表面表达。使用 pH 敏感超黄道素 pHluorin (SEP) 标记的突触后谷氨酸受体，包括 GluA1、GluA2、GluN1 和 GluN2A，我们发现巴弗洛霉素 A1、肉毒杆菌毒素 B、和/或破伤风毒素降低 SEP-GluA1、SEP-GluA2、SEP-GluN1 和 SEP-GluN2A 的 SEP 荧光。这些发现表明突触前囊泡胞吐作用抑制剂也会影响突触后表面表达的运输机制。最后，这项研究提供了深刻的见解，将突触前、突触后和星形胶质细胞的观点整合到使用这些突触囊泡胞吐抑制剂获得的数据的解释中。