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PMID:17703231

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Citation

Tan, FJ, Fire, AZ and Hill, RB (2007) Regulation of apoptosis by C. elegans CED-9 in the absence of the C-terminal transmembrane domain. Cell Death Differ. 14:1925-35

Abstract

Bcl-2 proteins regulate apoptosis in organisms as diverse as mammals and nematodes. These proteins are often localized at mitochondria by a C-terminal transmembrane domain. Although the transmembrane domain and mitochondrial localization are centrally involved in specific cases of vertebrate Bcl-2 activity, the significance of this localization is not clear for all species. Studying the Caenorhabditis elegans Bcl-2 homolog CED-9, we found that the transmembrane domain was both necessary and sufficient for localization at mitochondrial outer membranes. Furthermore, we found that in our assays, ced-9 transgenes lacking the transmembrane domain, although somewhat less active than equivalent transgenes derived from wild-type ced-9, rescued embryonic lethality of ced-9(lf) animals and responded properly to upstream signals in controlling the fate of Pn.aap neurons. Both of these apoptotic activities were retained in a construct where CED-9 lacking the transmembrane domain was targeted to the cytosolic surface of the endoplasmic reticulum and derived organelles, suggesting that in wild-type animals, accumulation at mitochondria is not essential for CED-9 to either inhibit or promote apoptosis in C. elegans. Taken together, these data are consistent with a multimodal character of CED-9 action, with an ability to regulate apoptosis through interactions in the cytosol coexisting with additional evolutionarily conserved role(s) at the membrane.

Links

PubMed PMC3047747 Online version:10.1038/sj.cdd.4402215

Keywords

Animals; Animals, Genetically Modified; Apoptosis; Caenorhabditis elegans/cytology; Caenorhabditis elegans/embryology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cytosol/metabolism; Embryonic Development; Mitochondrial Membranes/metabolism; Mitochondrial Membranes/ultrastructure; Muscles/cytology; Muscles/metabolism; Neurons/cytology; Organelles/metabolism; Protein Structure, Tertiary; Proto-Oncogene Proteins c-bcl-2/chemistry; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:CED9

located_in

GO:0005741: mitochondrial outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:CED9

part_of

GO:0005741: mitochondrial outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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