Article abstract

Nature Neuroscience 11, 799 - 806 (2008)
Published online: 8 June 2008 | doi:10.1038/nn.2135

Evolutionary expansion and anatomical specialization of synapse proteome complexity

Richard D Emes1,6, Andrew J Pocklington2,6, Christopher N G Anderson3,6, Alex Bayes3, Mark O Collins3, Catherine A Vickers4,5, Mike D R Croning3, Bilal R Malik2, Jyoti S Choudhary3, J Douglas Armstrong2 & Seth G N Grant3

Understanding the origins and evolution of synapses may provide insight into species diversity and the organization of the brain. Using comparative proteomics and genomics, we examined the evolution of the postsynaptic density (PSD) and membrane-associated guanylate kinase (MAGUK)-associated signaling complexes (MASCs) that underlie learning and memory. PSD and MASC orthologs found in yeast carry out basic cellular functions to regulate protein synthesis and structural plasticity. We observed marked changes in signaling complexity at the yeast-metazoan and invertebrate-vertebrate boundaries, with an expansion of key synaptic components, notably receptors, adhesion/cytoskeletal proteins and scaffold proteins. A proteomic comparison of Drosophila and mouse MASCs revealed species-specific adaptation with greater signaling complexity in mouse. Although synaptic components were conserved amongst diverse vertebrate species, mapping mRNA and protein expression in the mouse brain showed that vertebrate-specific components preferentially contributed to differences between brain regions. We propose that the evolution of synapse complexity around a core proto-synapse has contributed to invertebrate-vertebrate differences and to brain specialization.

  1. Institute for Science and Technology in Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK.
  2. Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, 5 Forrest Hill, Edinburgh EH1 2QL, UK.
  3. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  4. Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
  5. Okinawa Institute of Science and Technology, Neurobiology Research Unit, Suzaki, Uruma, Okinawa, Japan.
  6. These authors contributed equally to this work.

Correspondence to: Seth G N Grant3 e-mail:


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