RRC ID 55877
Author Ghose P, Rashid A, Insley P, Trivedi M, Shah P, Singhal A, Lu Y, Bao Z, Shaham S.
Title EFF-1 fusogen promotes phagosome sealing during cell process clearance in Caenorhabditis elegans.
Journal Nat Cell Biol
Abstract Phagocytosis of dying cells is critical in development and immunity1-3. Although proteins for recognition and engulfment of cellular debris following cell death are known4,5, 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 microenvironments6,7. Thus, such cells offer unique settings to explore engulfment programme mechanisms and specificity. Here, we report that dismantling and clearance of a morphologically complex Caenorhabditis elegans epithelial cell requires separate cell soma, proximal and distal process programmes. Similar compartment-specific events govern the elimination of a C. elegans neuron. Although 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 that promotes cell process clearance.
Volume 20(4)
Pages 393-399
Published 2018-4-1
DOI 10.1038/s41556-018-0068-5
PII 10.1038/s41556-018-0068-5
PMID 29556089
PMC PMC5876135
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Death Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Mutation Neurons / metabolism* Neurons / pathology Phagocytes / metabolism* Phagocytes / ultrastructure Phagocytosis* Phagosomes / genetics Phagosomes / metabolism* Phagosomes / ultrastructure Pseudopodia / genetics Pseudopodia / metabolism* Pseudopodia / ultrastructure Signal Transduction
IF 17.728
Times Cited 5
C.elegans tm2214 tm2423