Pyroptotic machinery in Annelida: functional characterization of gasdermin from Owenia fusiformis

Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis, an inflammatory lytic cell death critical for host defense. Although the evolutionary origin of GSDMs in Metazoa has been established, their presence in many invertebrate phyla, including Annelida, remains largely unknown. In this study, we identified a GSDM homolog, designated OfGSDME, from the annelid tubeworm Owenia fusiformis. OfGSDME harbors a pore-forming N-terminal domain capable of permeabilizing cell membranes and triggering pyroptotic cell death. Mechanistically, OfGSDME is cleaved and activated by OfCaspD and OfCaspF at the ₂₄₃DEVD₂₄₆ motif, releasing the OfGSDME-NT fragment that executes pyroptosis. Furthermore, OfGSDME-NT exhibits potent bactericidal activity against Escherichia coli. Collectively, this study establishes the presence of a functional pyroptotic GSDME in Annelida and provides insights into the function and evolution of the GSDM family.