Diversity in the intrinsic apoptosis pathway of nematodes

Young, Neil D; Harris, TJ; Evangelista, M; Tran, Sharon; Wouters, MA; Soares-da-Costa, Tatiana; Kershaw, NJ; Gasser, RB; Smith, Brian; Lee, Erinna; Fairlie, Walter

doi:10.1038/s42003-020-01208-5

Diversity in the intrinsic apoptosis pathway of nematodes

journal contribution

posted on 2025-01-22, 00:22 authored by Neil D Young, TJ Harris, M Evangelista, Sharon Tran, MA Wouters, Tatiana Soares-da-Costa, NJ Kershaw, RB Gasser, Brian SmithBrian Smith, Erinna LeeErinna Lee, Walter FairlieWalter Fairlie

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.

Funding

Research funding from the Australian Research Council (LP180101334 to N.D.Y., LP180101085 to R.B.G., DE190100806 to T.P.S.d.C. and FT150100212 to E.F.L) is gratefully acknowledged. T.P.S.C. also acknowledges support from the National Health and Medical Research Council of Australia (GNT1091976).

History

Publication Date

2020-08-28

Journal

Communications Biology

Volume

3

Article Number

478

Pagination

12p.

Publisher

Springer Nature

ISSN

2399-3642

Rights Statement

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