FIGURE 10:

A PtdIns(3)P-mediated signaling pathway that drives the degradation of apoptotic cells. (A) Diagram of the pathway. The phagocytic receptor CED-1 and its adaptor CED-6 recruit the large GTPase DYN-1 to phagosomal surfaces, an event resulting in the robust production of phagosomal PtdIns(3)P, which in turn recruits LST-4, SNX-1, and SNX-6 from cytosol to phagosomal surfaces. These PtdIns(3)P effectors act in two parallel and partially redundant pathways to induce the extension of membrane tubules from phagosomes. In addition, LST-4 interacts with DYN-1 (Dynamin) and stabilizes its association with phagosome, which recruits and stabilizes the association of RAB-7 with phagosomes. Both RAB-7 and phagosome tubules facilitate efficient endosomes/phagosome and lysosomes/phagosome fusions and ultimately result in the degradation of apoptotic cells. (B) A model indicating the two distinct PtdIns(3)P effector complexes on phagosomal surfaces. One complex include SNX-1 and SNX-6 (may also contain VPS-29), in which SNX-1 interacts with PtdIns(3)P and brings SNX-6 onto phagosomes. In the second complex, LST-4, perhaps as homodimers, interacts with both PtdIns(3)P and DYN-1, which are enriched on phagosomes, and stabilize the association of the whole complex with phagosomes. (C) Model proposing that the PtdIns(3)P effectors use their BAR domains to induce and/or stabilize the formation of phagosomal tubules, which facilitates the recruitment and fusion of intracellular organelles to phagosomes.