title: A post-synaptic scaffold at the origin of the animal kingdom.
abstract: BACKGROUND
  The evolution of complex sub-cellular structures such as the synapse requires the assembly of multiple proteins, each conferring added functionality to the integrated structure. Tracking the early evolution of synapses has not been possible without genomic information from the earliest branching animals. As the closest extant relatives to the Eumetazoa, Porifera (sponges) represent a pivotal group for understanding the evolution of nervous systems, because sponges lack neurons with clearly recognizable synapses, in contrast to eumetazoan animals.
  
  
  RESULTS
  We show that the genome of the demosponge Amphimedon queenslandica possesses a nearly complete set of post-synaptic protein homologs whose conserved interaction motifs suggest assembly into a complex structure. In the critical synaptic scaffold gene, dlg, residues that make hydrogen bonds and van der Waals interactions with the PDZ ligand are 100% conserved between sponge and human, as is the motif organization of the scaffolds. Expression in Amphimedon of multiple post-synaptic gene homologs in larval flask cells further supports the existence of an assembled structure. Among the few post-synaptic genes absent from Amphimedon, but present in Eumetazoa, are receptor genes including the entire ionotropic glutamate receptor family.
  
  
  CONCLUSIONS
  Highly conserved protein interaction motifs and co-expression in sponges of multiple proteins whose homologs interact in eumetazoan synapses indicate that a complex protein scaffold was present at the origin of animals, perhaps predating nervous systems. A relatively small number of crucial innovations to this pre-existing structure may represent the founding changes that led to a post-synaptic element.
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Onur
authors.initials: O
authors.lastname: Sakarya
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Armstrong
authors.forename: Maja
authors.initials: M
authors.lastname: Adamska
authors.forename: Marcin
authors.initials: M
authors.lastname: Adamski
authors.forename: I-Fan
authors.initials: IF
authors.lastname: Wang
authors.forename: Bruce
authors.initials: B
authors.lastname: Tidor
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Degnan
authors.forename: Todd H
authors.initials: TH
authors.lastname: Oakley
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011161:Porifera / Q000235:genetics*; D013569:Synapses / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins