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

Abstract

Engulfment of apoptotic cells in Caenorhabditis elegans is controlled by two 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 the engulfment of dying cells and in the migrations of the two distal tip cells of the developing gonad. Here we find that ced-2 and ced-10 encode proteins similar to the human adaptor protein CrkII and the human GTPase Rac, respectively. Together with the previous observation that ced-5 encodes a protein similar to human DOCK180, our findings define a signalling pathway that controls phagocytosis and cell migration. We provide evidence that CED-2 and CED-10 function in engulfing rather than dying cells to control the phagocytosis of cell corpses, that CED-2 and CED-5 physically interact, and that ced-10 probably functions downstream of ced-2 and ced-5. We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces.

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Figure 1: The distal tip cell (DTC) reverses its direction of migration in a ced-2 mutant.
Figure 2: ced-2 and ced-10 encode proteins similar to human CrkII and Rac, respectively.
Figure 3: CED-2 and CED-5 interact.
Figure 4: Model for the control of phagocytosis in programmed cell death by ced-2, ced-5 and ced-10.

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Acknowledgements

We thank B. Hersh and R. Ranganathan for comments concerning this manuscript, and Y. Kohara for providing cDNA clones. P.W.R. was supported by a National Science Foundation Fellowship and an NIH training grant. H.R.H. is an Investigator of the Howard Hughes Medical Institute.

Correspondence and requests for materials should be addressed to H.R.H. The nucleotide sequences of ced-2 and ced-10 have been deposited at GenBank under accession numbers AF226866 and AF226867, respectively.

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Correspondence to H. Robert Horvitz.

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Reddien, P., Horvitz, H. CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol 2, 131–136 (2000). https://doi.org/10.1038/35004000

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