Figure 5.

Phagocytosis and LAP pathways where PIK3C3 complexes and NRBF2 are involved. In phagocytosis, the closed phagosome first fuses with early endosomes to become the early phagosome marked by RAB5. The early phagosome matures into the late phagosome, and it eventually fuses with lysosomes to become the phagolysosome (maturation), then the particle is degraded. Similar to the endocytic pathway, RAB5 recruits complex II to the early phagosome, and the RAB5-RAB7 transition is mediated by the MON1-CCZ1 complex. In LAP, complex II and RUBCN/Rubicon are recruited to the closed phagosome (LAPosome, step1), where RUBCN is essential for the recruitment of complex II. In contrast to phagocytosis, the complex II- RUBCN complex is required for the recruitment of RAB5 [74]. The PtdIns3P synthesized by the complex II- RUBCN complex recruits the NOX2 complex, which synthesizes ROS from NADPH on the LAPosome (step2). This is followed by LC3 lipidation (step 3). Along with LC3-II [74], RAB7 activated by the MON1-CCZ1 complex facilitates LAPosome fusion with lysosomes (maturation) to degrade the particle. In BMDM from mice, NRBF2 is required for the maturation step of LAP by facilitating the GEF activity of the MON1-CCZ1 complex to activate RAB7