EFF-1 fusogen promotes phagosome sealing during cell process clearance in C. elegans

Phagocytosis of dying cells is critical in development and immunity(1–3). While proteins for recognition and engulfment of cellular debris following cell death are known(4,5), proteins that directly mediate phagosome sealing are uncharacterized. Furthermore, whether all phagocytic targets are cleared using the same machinery is unclear. Degeneration of morphologically-complex cells, such as neurons, glia, and melanocytes, produces phagocytic targets of various shapes and sizes located in different microenvironments(6,7). Such cells, therefore, offer unique settings to explore engulfment program mechanisms and specificity. Here we report that dismantling and clearance of a morphologically-complex C. elegans epithelial cell requires separate cell-soma, proximal-, and distal-process programs. Similar compartment-specific events govern elimination of a C. elegans neuron. While canonical engulfment proteins drive cell-soma clearance, these are not required for process removal. We find that EFF-1, a protein previously implicated in cell-cell fusion(8), specifically promotes distal-process phagocytosis. EFF-1 localizes to phagocyte pseudopod tips, and acts exoplasmically to drive phagosome sealing. eff-1 mutations result in phagocytosis arrest with unsealed phagosomes. Our studies suggest universal mechanisms for dismantling morphologically-complex cells, and uncover a phagosome sealing component promoting cell-process clearance.