Institute of Physiology and Pathophysiology, Department of Molecular Cell Physiology, Philipps-University Marburg, 35037 Marburg, Germany.
J Cell Sci. 2023 Mar 15;136(6). doi: 10.1242/jcs.260366. Epub 2023 Mar 5.
Exocytosis is a fundamental cellular process by which cells secrete cargos from their apical membrane into the extracellular lumen. Cargo release proceeds in sequential steps that depend on coordinated assembly and organization of an actin cytoskeletal network. Here, we identified the conserved actin-crosslinking protein Swip-1 as a novel regulator controlling exocytosis of glue granules in the Drosophila salivary gland. Real-time imaging revealed that Swip-1 is simultaneously recruited with F-actin onto secreting granules in proximity to the apical membrane. We observed that Swip-1 is rapidly cleared at the point of secretory vesicle fusion and colocalizes with actomyosin network around the fused vesicles. Loss of Swip-1 function impairs secretory cargo expulsion, resulting in strongly delayed secretion. Thus, our results uncover a novel role of Swip-1 in secretory vesicle compression and expulsion of cargo during regulated exocytosis. Remarkably, this function neither requires Ca2+ binding nor dimerization of Swip-1. Our data rather suggest that Swip-1 regulates actomyosin activity upstream of Rho-GTPase signaling to drive proper vesicle membrane crumpling and expulsion of cargo.
胞吐作用是一种基本的细胞过程，通过该过程细胞将货物从其顶端膜分泌到细胞外腔中。货物释放是通过依赖于肌动蛋白细胞骨架网络的协调组装和组织的连续步骤进行的。在这里，我们鉴定了保守的肌动蛋白交联蛋白 Swip-1 作为一种新的调节剂，控制果蝇唾液腺中胶粒的胞吐作用。实时成像显示，Swip-1 与 F-肌动蛋白同时被招募到靠近顶端膜的分泌颗粒上。我们观察到，Swip-1 在分泌小泡融合点迅速清除，并与融合小泡周围的肌动球蛋白网络共定位。Swip-1 功能的丧失会损害分泌货物的排出，导致分泌严重延迟。因此，我们的结果揭示了 Swip-1 在调节性胞吐作用期间参与分泌小泡压缩和货物排出的新作用。值得注意的是，这种功能既不需要 Swip-1 的 Ca2+结合，也不需要二聚化。我们的数据表明，Swip-1 在 Rho-GTPase 信号的上游调节肌动球蛋白活性，以驱动适当的囊泡膜褶皱和货物排出。
