RT Journal Article SR Electronic T1 The CARD-CC/Bcl10/paracaspase signaling complex is functionally conserved since the last common ancestor of Planulozoa JF bioRxiv FD Cold Spring Harbor Laboratory SP 046789 DO 10.1101/046789 A1 Jens Staal A1 Yasmine Driege A1 Alice Borghi A1 Paco Hulpiau A1 Laurens Lievens A1 Ismail Sahin Gul A1 Srividhya Sundararaman A1 Amanda Gonçalves A1 Ineke Dhondt A1 Bart P. Braeckman A1 Ulrich Technau A1 Yvan Saeys A1 Frans van Roy A1 Rudi Beyaert YR 2016 UL http://biorxiv.org/content/early/2016/12/29/046789.abstract AB Type 1 paracaspases originated in the Ediacaran geological period before the last common ancestor of bilaterians and cnidarians (Planulozoa). Cnidarians have several paralog type 1 paracaspases, type 2 paracaspases, and a homolog of Bcl10. Notably in bilaterians, lineages like nematodes and insects lack Bcl10 whereas other lineages such as vertebrates, hemichordates, annelids and mollusks have a Bcl10 homolog. 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 cnidarians, nematodes and mice also suggest an ancient neuronal role for the type 1 paracaspases.