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C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180
1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Abstract:
During programmed cell death, cell corpses are rapidly engulfed. This engulfment process involves the recognition and subsequent phagocytosis of cell corpses by engulfing cells. How cell corpses are engulfed is largely unknown. Here we report that ced-5, a gene that is required for cell-corpse engulfment in the nematode Caenorhabditis elegans, encodes a protein that is similar to the human protein DOCK180 and the Drosophila melanogaster protein Myoblast City (MBC), both of which have been implicated in the extension of cell surfaces. ced-5 mutants are defective not only in the engulfment of cell corpses but also in the migrations of two specific gonadal cells, the distal tip cells. The expression of human DOCK180 in C. elegans rescued the cell-migration defect of a ced-5 mutant. We present evidence that ced-5 functions in engulfing cells during the engulfment of cell corpses. We suggest that ced-5 acts in the extension of the surface of an engulfing cell around a dying cell during programmed cell death. We name this new family of proteins that function in the extension of cell surfaces the CDM (for CED-5, DOCK180 and MBC) family.
Insights
The gene ced-5 is crucial for engulfing dying cells during programmed cell death. This discovery identifies a new protein family, CDM, involved in cell surface extension for engulfment.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Programmed cell death (apoptosis) requires efficient removal of cell corpses.
- The mechanisms governing cell corpse engulfment are not fully understood.
- The gene ced-5 in Caenorhabditis elegans is known to be essential for engulfment.
Purpose of the Study:
- To elucidate the molecular mechanism of cell corpse engulfment.
- To identify the function and protein family associated with ced-5.
- To understand ced-5's role in cellular processes beyond engulfment.
Main Methods:
- Genetic analysis of ced-5 mutants in Caenorhabditis elegans.
- Protein sequence homology analysis comparing ced-5 to known proteins.
- Functional rescue experiments using human DOCK180 in C. elegans.
Main Results:
- Ced-5 protein is homologous to human DOCK180 and Drosophila Myoblast City (MBC).
- ced-5 mutants exhibit defects in both cell corpse engulfment and distal tip cell migration.
- Human DOCK180 expression rescued the cell migration defect in ced-5 mutants.
- Evidence suggests ced-5 acts in the engulfing cell, mediating cell surface extension.
Conclusions:
- Ced-5 plays a critical role in the engulfment of cell corpses by facilitating the extension of the engulfing cell's surface.
- A new protein family, the CDM family (CED-5, DOCK180, MBC), is identified, involved in cell surface extension.
- Ced-5's function in cell migration highlights its broader role in cellular morphogenesis.