Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1

Two important biological events happen coincidently soon after nerve injury in the peripheral nervous system in C. elegans: removal of axon debris and initiation of axon regeneration. But, it is not known how these two events are co-regulated. Mutants of ced-1, a homolog of Draper and MEGF10, display defects in both events. One model is that those events could be related. But our data suggest that they are actually separable. CED-1 functions in the muscle-type engulfing cells in both events and is enriched in muscle protrusions in close contact with axon debris and regenerating axons. Its two functions occur through distinct biochemical mechanisms; extracellular domain-mediated adhesion for regeneration and extracellular domain binding-induced intracellular domain signaling for debris removal. These studies identify CED-1 in engulfing cells as a receptor in debris removal but as an adhesion molecule in neuronal regeneration, and have important implications for understanding neural circuit repair after injury.
It is unclear how removal of axon debris and initiation of axon regeneration following nerve injury is co-regulated. In this study, the authors show that the extracellular domain (ECD) of the engulfment receptor, CED-1, functions as an adhesion molecule to promote axonal regeneration after injury, independent of its function in phagocytosis