TY - JOUR T1 - The Bcl10/paracaspase signalling complex is functionally conserved since the last common ancestor of planulozoa JF - bioRxiv DO - 10.1101/046789 SP - 046789 AU - Jens Staal AU - Yasmine Driege AU - Paco Hulpiau AU - Rudi Beyaert Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/04/15/046789.abstract N2 - CARMA – CARDs, a single MALT1, cleavage and CLAP: an old story. The type 1 paracaspases are defined by their domain composition with an N-terminal Death-domain, immunoglobulin domains and a caspase-like (paracaspase) domain. 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 (CLAP). Notably in bilaterans, lineages like nematodes and insects lack Bcl10 whereas other lineages such as vertebrates, hemichordates, annelids and molluscs 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 (CBM) complex. There 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 two ancestral type 1 paracaspase paralogs in the bilateran last common ancestor, where 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 Bcl10/paracaspase signalling complex. ER -