Agonist-mediated stimulated pathway of mucin and insulin release are biphasic in which rapid fusion of pre-docked granules is followed by slow docking and fusion of granules from the reserve pool. Here, based on a cell-culture system, we show that plasma membrane-located tetraspanin-8 sequesters syntaxin-2 to control mucin release. Tetraspanin-8 affects fusion of granules during the second phase of stimulated mucin release. The tetraspanin-8/syntaxin-2 complex does not contain VAMP-8, which functions with syntaxin-2 to mediate granule fusion. We suggest that by sequestering syntaxin-2, tetraspanin-8 prevents docking of granules from the reserve pool. In the absence of tetraspanin-8, more syntaxin-2 is available for docking and fusion of granules and thus doubles the quantities of mucins secreted. This principle also applies to insulin release and we suggest a cell type specific Tetraspanin/Syntaxin combination is a general mechanism regulating the fusion of dense core granules.

激动剂介导的粘蛋白和胰岛素释放的刺激途径是双相的，其中预对接颗粒的快速融合随后是来自储备库的颗粒的缓慢对接和融合。在这里，基于细胞培养系统，我们证明位于质膜的 tetraspanin-8 隔离 Syntaxin-2 以控制粘蛋白释放。Tetraspanin-8 在刺激粘蛋白释放的第二阶段影响颗粒的融合。tetraspanin-8/syntaxin-2 复合物不含 VAMP-8，VAMP-8 与 syntaxin-2 一起发挥作用以介导颗粒融合。我们建议通过隔离 Syntaxin-2，tetraspanin-8 可以防止颗粒与储备池对接。在缺乏 tetraspanin-8 的情况下，更多的 Syntaxin-2 可用于颗粒的对接和融合，从而使分泌的粘蛋白数量加倍。这一原理也适用于胰岛素释放，我们认为细胞类型特异性四跨膜蛋白/突触蛋白组合是调节致密核心颗粒融合的一般机制。