EFhD2/Swip-1 promotes exocytosis of glue granules in the exocrine Drosophila salivary gland.

Exocytosis is a fundamental cellular process by which cells secret cargos from their apical membrane into the extracellular lumen. Cargo release proceeds in sequential steps that depend on a coordinated assembly and organization of an actin cytoskeletal network. Here, we identified the conserved actin-crosslinking protein EFhD2/Swip-1 as a novel regulator controlling exocytosis of glue granules in the Drosophila salivary gland. Real-time imaging revealed that EFhD2/Swip-1 is simultaneously recruited with F-actin onto secreting granules in proximity to the apical membrane. EFhD2/Swip-1 is rapidly cleared at the point of secretory vesicle fusion and colocalizes with actomyosin network around the fused vesicles. Loss of EFhD2/Swip-1 function impairs secretory cargo expulsion resulting in strongly delayed secretion. Thus, our results uncover a novel role of EFhD2/Swip-1 in secretory vesicle compression and expulsion of cargo during regulated exocytosis. Remarkably, this function neither require calcium-binding nor dimerization of EFhD2/Swip-1. Our data rather suggest that EFhD2/Swip-1 regulates actomyosin activity upstream of Rho-GTPase signaling to drive proper vesicle membrane crumpling and expulsion of cargo.