GEI-17-Mediated SUMOylation of GDI-1 Regulates Apoptotic Cell Clearance

Apoptotic cell clearance represents the final stage of apoptosis, and involves phagosome formation, maturation, and digestion. Here, we found that SUMO modifications participate in apoptotic cell clearance by influencing phagosomal degradation activity in C. elegans. The SUMO E3 ligase, GEI-17, SUMOylates GDP dissociation inhibitor (GDI-1) at K270 to trigger phagosomal degradation. Upon SUMOylation, GDI-1 facilitates release of GDP-bound RAB-1, which is subsequently converted to the GTP-bound form in a manner dependent on GDI displacement factor, PRAF-3. RAB-1 conversion enables binding and translocation of RAB-7 from the endoplasmic reticulum to Golgi to promote phagosome maturation and degradation activity. In the absence of GDI-1 SUMOylation, GDI-1 binds to GDP-RAB-1, sequestering it in the cytoplasm, resulting in impaired phagosomal degradation. Furthermore, we found SUMOylation of GDI1 at a conserved site plays a crucial role in efferocytosis regulation in mammals. This study defines a previously unrecognized mechanism by which SUMOylation drives apoptotic cell clearance.