Functional conservation of the apoptotic machinery from coral to man: the diverse and complex Bcl-2 and caspase repertoires of Acropora millepora

Abstract

BackgroundApoptotic cell death is a defining and ubiquitous characteristic of metazoans, but its evolutionary origins are unclear. Although Caenorhabditis and Drosophila played key roles in establishing the molecular bases of apoptosis, it is now clear that cell death pathways of these animals do not reflect ancestral characteristics. Conversely, recent work suggests that the apoptotic networks of cnidarians may be complex and vertebrate-like, hence characterization of the apoptotic complement of representatives of the basal cnidarian class Anthozoa will help us to understand the evolution of the vertebrate apoptotic network.ResultsWe describe the Bcl-2 and caspase protein repertoires of the coral Acropora millepora, making use of the comprehensive transcriptomic data available for this species. Molecular phylogenetics indicates that some Acropora proteins are orthologs of specific mammalian pro-apoptotic Bcl-2 family members, but the relationships of other Bcl-2 and caspases are unclear. The pro- or anti-apoptotic activities of coral Bcl-2 proteins were investigated by expression in mammalian cells, and the results imply functional conservation of the effector/anti-apoptotic machinery despite limited sequence conservation in the anti-apoptotic Bcl-2 proteins. A novel caspase type (“Caspase-X”), containing both inactive and active caspase domains, was identified in Acropora and appears to be restricted to corals. When expressed in mammalian cells, full-length caspase-X caused loss of viability, and a truncated version containing only the active domain was more effective in inducing cell death, suggesting that the inactive domain might modulate activity in the full-length protein. Structure prediction suggests that the active and inactive caspase domains in caspase-X are likely to interact, resulting in a structure resembling that of the active domain in procaspase-8 and the inactive caspase domain in the mammalian c-FLIP anti-apoptotic factor.ConclusionsThe data presented here confirm that many of the basic mechanisms involved in both the intrinsic and extrinsic apoptotic pathways were in place in the common ancestor of cnidarians and bilaterians. With the identification of most or all of the repertoires of coral Bcl-2 and caspases, our results not only provide new perspectives on the evolution of apoptotic pathways, but also a framework for future experimental studies towards a complete understanding of coral bleaching mechanisms, in which apoptotic cell death might be involved.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2355-x) contains supplementary material, which is available to authorized users.

Hydra Bcl-2 and TMBIMP family proteins display anti-apoptotic functions

“…In accordance with these published data a recent search in available sequencing data from Hydra has now revealed 9 genes encoding Bcl--2--like proteins and two encoding Bak--like proteins. This gene family was also found recently to be present in corals of the genus Acropora ( (Moya et al, 2016)). The Hydra proteins that we had previously studied were associated with membranes, five with mitochondria--and two with ER--membranes.…”

Caspases from Scleractinian Coral Show Unique Regulatory Features

“…Caspase-8-like proteins containing DED motifs would also activate the executioner (and PaCasp3 or OfCasp3b) indirectly. The putative caspase-8 and caspase-3executioner proteins have been identified, but not yet characterized, in coral (25,(61)(62)(63). In addition, PIDDosome complex proteins are also present in coral (64).…”

Viruses and the origin of microbiome selection and immunity

“…However, metazoan apoptosis appears to be unique through its use of TNF receptors (Quistad and Traylor-Knowles, 2016), which are activated by TNF ligands (Aggarwal, 2003). Many of the domains involved with apoptotic signaling via TNF receptors are also present and functional in cnidarians, considered to be among the oldest animal phyla (Lasi et al, 2010;Quistad et al, 2014;Sakamaki et al, 2014Sakamaki et al, , 2015Lu et al, 2016;Moya et al, 2016).…”