The trafficking of aquaporin 5 (AQP5) is critical for salivary secretion. Synaptosomal-associated protein 23 (SNAP23) is an important regulator in the process of membrane fusion. However, the role of SNAP23 on AQP5 trafficking has not been explored. Botulinum toxin type A (BoNT/A) is a bacterial toxin that effectively treats sialorrhea. We previously reported that BoNT/A induced AQP5 redistribution in cultured acinar cells, but the mechanism remained unclear. In this study, SNAP23 was predominantly localized to the plasma membrane of acinar cells in the rat submandibular gland (SMG) and colocalized with AQP5 at the apical membrane of acinar cells. In stable GFP-AQP5-transfected SMG-C6 cells, the acetylcholine receptor agonist carbachol (CCh) induced trafficking of AQP5 from intracellular vesicles to the apical membrane. Furthermore, SNAP23 knockdown by siRNA significantly inhibited CCh-induced AQP5 trafficking, whereas this inhibitory effect was reversed by SNAP23 re-expression, indicating that SNAP23 was essential in AQP5 trafficking. More importantly, BoNT/A inhibited salivary secretion from SMGs, and the underlying mechanism involved that BoNT/A blocked CCh-triggered AQP5 trafficking by decreasing SNAP23 in acinar cells. Taken together, these results identified a crucial role for SNAP23 in AQP5 trafficking and provided new insights into the mechanism of BoNT/A in treating sialorrhea and thereby a theoretical basis for clinical applications.

中文翻译：

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a 型肉毒杆菌毒素通过减少颌下腺泡细胞中的突触体相关蛋白 23 来阻断水通道蛋白 5 的运输

水通道蛋白 5 (AQP5) 的运输对于唾液分泌至关重要。突触体相关蛋白23（SNAP23）是膜融合过程中的重要调节因子。然而，SNAP23 在 AQP5 贩运中的作用尚未被探索。 A 型肉毒杆菌毒素 (BoNT/A) 是一种细菌毒素，可有效治疗流涎。我们之前报道过 BoNT/A 在培养的腺泡细胞中诱导 AQP5 重新分布，但其机制仍不清楚。在这项研究中，SNAP23 主要定位于大鼠颌下腺 (SMG) 腺泡细胞的质膜，并与 AQP5 共定位于腺泡细胞的顶膜。在稳定的 GFP-AQP5 转染的 SMG-C6 细胞中，乙酰胆碱受体激动剂卡巴胆碱 (CCh) 诱导 AQP5 从细胞内囊泡转运至顶膜。此外，通过siRNA敲低SNAP23可显着抑制CCh诱导的AQP5运输，而这种抑制作用可通过SNAP23重新表达而逆转，表明SNAP23在AQP5运输中至关重要。更重要的是，BoNT/A 抑制 SMG 的唾液分泌，其潜在机制涉及 BoNT/A 通过减少腺泡细胞中的 SNAP23 来阻断 CCh 触发的 AQP5 运输。总而言之，这些结果确定了 SNAP23 在 AQP5 运输中的关键作用，并为 BoNT/A 治疗流涎的机制提供了新的见解，从而为临床应用提供了理论基础。