CED-2/Crkll and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans

Engulfment of apoptotic cells in Caenorhabditis elegans is controlled by tw o partially redundant pathways. Mutations in genes in one of these pathways , defined by the genes ced-2, ced-5 and ced-10, result in defects both in t he engulfment of dying cells and in the migrations of the two distal tip ce lls of the developing gonad. Here we find that ced-2 and ced-10 encode prot eins similar to the human adaptor protein Crkll and the human GTPase Rac, r espectively. Together with the previous observation that ced-5 encodes a pr otein similar to human DOCK180, our findings define a signalling pathway th at controls phagocytosis and cell migration. We provide evidence that CED-2 and CED-10 function in engulfing rather than dying cells to control the ph agocytosis of cell corpses, that CED-2 and CED-5 physically interact, and t hat ced-10 probably functions downstream of ced-2 and ced-5. We propose tha t CED-2/Crkll and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces.