Diversity in the intrinsic apoptosis pathway of nematodes

• Published in: Communications biology Vol. 3; no. 1; p. 478
• Main Authors: Young, Neil D., Harris, Tiffany J., Evangelista, Marco, Tran, Sharon, Wouters, Merridee A., Soares da Costa, Tatiana P., Kershaw, Nadia J., Gasser, Robin B., Smith, Brian J., Lee, Erinna F., Fairlie, W. Douglas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.08.2020; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/109; 13/2; 13/31; 631/181/735; 631/80/82; Apaf-1 protein; Apoptosis; BAX protein; Bcl-2 protein; Biology; Biomedical and Life Sciences; Life Sciences; Nematodes; Proteins; Worms
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-01208-5

Early studies of the free-living nematode C. elegans informed us how BCL-2-regulated apoptosis in humans is regulated. However, subsequent studies showed C. elegans apoptosis has several unique features compared with human apoptosis. To date, there has been no detailed analysis of apoptosis regulators in nematodes other than C. elegans . Here, we discovered BCL-2 orthologues in 89 free-living and parasitic nematode taxa representing four evolutionary clades (I, III, IV and V). Unlike in C. elegans , 15 species possess multiple (two to five) BCL-2-like proteins, and some do not have any recognisable BCL-2 sequences. Functional studies provided no evidence that BAX/BAK proteins have evolved in nematodes, and structural studies of a BCL-2 protein from the basal clade I revealed it lacks a functionally important feature of the C. elegans orthologue. Clade I CED-4/APAF-1 proteins also possess WD40-repeat sequences associated with apoptosome assembly, not present in C. elegans , or other nematode taxa studied. Young et al. report on the diversity in regulation of nematode apoptosis. Results indicate that the apoptotic pathways of C. elegans are not fully representative of nematodes generally.