Cells use non-canonical forms of autophagy to clear cell corpses and cell fragments, including processes such as LC3-associated phagocytosis (LAP)1. We have been studying the clearance of two native LAP cargos in Caenorhabditis elegans embryos, including a cell fragment derived from the final step of cytokinesis called the midbody remnant2,3 and a cell that undergoes programmed necrosis after fertilization called the polar body4. Exposure of the lipid phosphatidylserine on these cell corpses and cell debris recruits engulfment receptor CED-1 to the plasma membrane. Receptor trafficking depends on the PI3Kinase VPS-34, RAB-5 GTPase, and the sorting nexin SNX-6. Receptor-mediated engulfment pathways converge on the Rac1 ortholog CED-10 to drive actin polymerization and extend the plasma membrane to engulf cell corpses and cell debris in a phagosome. Rab GTPases and LC3 homologs LGG-1 and LGG-2 are sequentially recruited to the phagosome membrane, which also depends on the PI3Kinase VPS-34. RAB-7 GTPase is required for lysosome recruitment to the phagosome, while LC3 lipidation promotes degradation of the corpse membrane inside the phagolysosome. After membrane breakdown, the polar body phagolysosome tubulates into small vesicles in an mTOR- (LET-363) and ARL-8-dependent manner, which facilitates its timely degradation. These genetic model systems reveal insights into the mechanisms of phagocytosis, LC3-associated phagosome maturation and phagolysosomal degradation, expanding the repertoire of cargos degraded by non-canonical autophagy in vivo. References: 1. Safely removing cell debris with LC3-associated phagocytosis. Fazeli G, Wehman AM. Biol Cell. 2017 Oct;109(10):355-363. 2. C. elegans midbodies are released, phagocytosed and undergo LC3-dependent degradation independent of macroautophagy. Fazeli G, Trinkwalder M, Irmisch L, Wehman AM. J Cell Sci. 2016 Oct 15;129(20):3721-3731. 3. Rab GTPases mature the LC3-associated midbody phagosome. Fazeli G, Wehman AM. Commun Integr Biol. 2017; 10(2):
e1297349. 4. C. elegans Blastomeres Clear the Corpse of the Second Polar Body by LC3-Associated Phagocytosis. Fazeli G, Stetter M, Lisack JN, Wehman AM. Cell Rep. 2018 May 15;23(7):2070-2082.