Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6
1Cold Spring Harbor Laboratory, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Institute of Health, Cold Spring Harbor, Bethesda, 11724, 20892, USA.
Abstract:
The rapid engulfment of apoptotic cells is a specialized innate immune response used by organisms to remove apoptotic cells. In mammals, several receptors that recognize apoptotic cells have been identified; molecules that transduce signals from these receptors to downstream cytoskeleton molecules have not been found, however [1] [2] [3]. Our previous analysis of the engulfment gene ced-6 in Caenorhabditis elegans has suggested that CED-6 is an adaptor protein that participates in a signal transduction pathway that mediates the specific recognition and engulfment of apoptotic cells [1]. Here, we describe our isolation and characterization of a human cDNA encoding a protein, hCED-6, with strong sequence similarity to C. elegans CED-6. As is the case with the worm protein, hCED-6 contains a phosphotyrosine-binding (PTB) domain and potential Src-homology domain 3 (SH3) binding sites. Both CED-6 and hCED-6 contain a predicted coiled-coil domain in the middle region. The hCED-6 protein lacks the extended carboxyl terminus found in worm CED-6; this carboxy-terminal extension appears not to be essential for CED-6 function in C. elegans, however. Overexpression of hCED-6 rescues the engulfment defect of ced-6 mutants in C. elegans significantly, suggesting that hCED-6 is a functional homologue of C. elegans CED-6. Human ced-6 is expressed widely in most human tissues. Thus, CED-6, and the CED-6 signal transduction pathway, might be conserved from C. elegans to humans and are present in most, if not all, human tissues.
Insights
Scientists identified a human protein, hCED-6, that functions similarly to a C. elegans protein in clearing apoptotic cells. This discovery suggests a conserved pathway for cell corpse removal across species.
Area of Science:
- Cell biology
- Immunology
- Genetics
Background:
- Apoptotic cell engulfment is a crucial innate immune process for tissue homeostasis.
- Mammalian receptors for apoptotic cells are known, but downstream signaling molecules remain elusive.
- The Caenorhabditis elegans CED-6 protein acts as an adaptor in apoptotic cell engulfment.
Purpose of the Study:
- To isolate and characterize a human homolog of the C. elegans CED-6 gene.
- To investigate the functional conservation of CED-6 between C. elegans and humans.
- To determine the expression pattern of human CED-6.
Main Methods:
- Isolation and characterization of human cDNA encoding hCED-6.
- Sequence analysis of hCED-6, identifying conserved domains (PTB, SH3 binding sites, coiled-coil).
- Functional rescue experiments in C. elegans ced-6 mutants by overexpressing hCED-6.
Main Results:
- A human cDNA encoding hCED-6 with significant sequence similarity to C. elegans CED-6 was identified.
- hCED-6 possesses conserved functional domains, including a PTB domain.
- Overexpression of hCED-6 successfully rescued the engulfment defects in C. elegans ced-6 mutants, indicating functional homology.
- Human ced-6 is expressed broadly across most human tissues.
Conclusions:
- hCED-6 is a functional homolog of C. elegans CED-6, suggesting conserved mechanisms for apoptotic cell engulfment.
- The CED-6-mediated signal transduction pathway may be conserved from invertebrates to humans.
- The widespread expression of human CED-6 implies its importance in various human tissues.
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