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The CARD-CC/Bcl10/paracaspase signaling complex is functionally conserved since the last common ancestor of planulozoa.
Bart P. Braeckman,
Frans Van Roy,
Posted 02 Apr 2016
bioRxiv DOI: 10.1101/046789 (published DOI: 10.3389/fimmu.2018.01136)
Posted 02 Apr 2016
Type 1 paracaspases originated in the Ediacaran geological period before the last common ancestor of bilaterans and cnidarians (planulozoa). Cnidarians have several paralog type 1 paracaspases, type 2 paracaspases, and a homolog of Bcl10. Notably in bilaterans, lineages like nematodes and insects lack Bcl10 whereas other lineages such as vertebrates, hemichordates, annelids and mollusks do contain Bcl10. A survey of invertebrate CARD-coiled-coil (CC) domain homologs of CARMA/CARD9 revealed such homologs only in species with Bcl10, indicating an ancient co-evolution of the entire CARD-CC/Bcl10/MALT1-like paracaspase (CBM) complex. Furthermore, vertebrate-like Syk/Zap70 tyrosine kinase homologs with the ITAM-binding SH2 domain were found in invertebrate organisms with CARD-CC/Bcl10, indicating that this pathway might be the original user of the CBM complex. We also established that the downstream signaling proteins TRAF2 and TRAF6 are functionally conserved in cnidaria. There also seems to be a correlation where invertebrates with CARD-CC and Bcl10 have type 1 paracaspases which are more similar to the paracaspases found in vertebrates. A proposed evolutionary scenario includes at least two ancestral type 1 paracaspase paralogs in the planulozoan last common ancestor, where at least one paralog usually is dependent on CARD-CC/Bcl10 for its function. Functional analyses of invertebrate type 1 paracaspases and Bcl10 homologs support this scenario and indicate an ancient origin of the CARD-CC/Bcl10/paracaspase signaling complex. Results from cnidaria, nematodes and mice also suggest an ancient neuronal role for the type 1 paracaspases.
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