SRGP-1 regulation, targets, and contribution to cell killing in C. elegans

The engulfment of apoptotic cell corpses is an evolutionary conserved process used by multicellular systems to remove cells with inappropriate potential (e.g., self-reactive T-cells, potentially cancerous cells). Neighboring or specialized phagocytic cells remove cell corpses through distinct steps: they first recognize the cell on the verge of death, then reorchestrate their cellular architecture toward it, actively contribute to cell killing, and eventually engulf the corpse. Thus engulfment signaling must be tightly controlled to maintain tissue homeostasis. Signaling cascades mediating cell corpse clearance likely converge at the level of the small GTPase CED-10 (Rac1); given this key position, CED-10 must be subject to a tight regulatory mechanism to prevent inappropriate phagocytic events. Here, we discuss recent work characterizing srgp-1 (nematode ortholog of mammalian srGAP), a candidate GTPase activating protein (GAP) for CED-10 involved in cell corpse clearance and "sick" cell killing in C. elegans. We additionally discuss several possible determinants of SRGP-1 function, contributing to either SRGP-1 localization and/or activation. We also survey other potential candidate GTPases that might contribute to cell corpse clearance in C. elegans, and eventually recapitulate the role of engulfment during cell killing.