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Cited by 291Marine Invertebrate Physiology and EcologyNeuroscience and Neuropharmacology ResearchDevelopmental Biology and Gene Regulation

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A Post-Synaptic Scaffold at the Origin of the Animal Kingdom

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Sakarya, Onur, Armstrong, Kathryn A., Adamska, Maja, Adamski, Marcin, Wang, I-Fan, Tidor, Bruce, Degnan, Bernard M., Oakley, Todd H., Kosik, Kenneth S.·2007·PLoS ONE
DOI 10.1371/journal.pone.0000506PMC PMC1876816
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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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

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Figure 1 Origination periods of post-synaptic genes. One possible configuration of the post-synaptic genes based on the known organization of the post-synaptic junction is illustrated. Each color represents the origination period (figure inset) of the gene family inferred from phylogenetic analyses (Figure S1). As further evidence for orthology, domain architectures of selected gene family members were compared (Figure S2). NCBI accession numbers for each gene family member are provided in Table S1. Some gene families may have been lost from the investigated genomes and originated with an earlier ancestor than shown. Question mark indicates insufficient traces to confirm this PDZ domain.
Figure 1 Origination periods of post-synaptic genes. One possible configuration of the post-synaptic genes based on the known organization of the post-synaptic junction is illustrated. Each color represents the origination period (figure inset) of the gene family inferred from phylogenetic analyses (Figure S1). As further evidence for orthology, domain architectures of selected gene family members were compared (Figure S2). NCBI accession numbers for each gene family member are provided in Table S1. Some gene families may have been lost from the investigated genomes and originated with an earlier ancestor than shown. Question mark indicates insufficient traces to confirm this PDZ domain.CC BY · PubMed Central
Figure 2 (A) Sponge PDZ3—CRIPT Homology Model. The last five residues of the CRIPT protein (yellow) interact with PDZ3 residues (blue and orange) by making van der Waals contacts, hydrogen bonds, or electrostatic interactions of greater than 0.1 kcal/mol in magnitude in any of the PDZ3 homology models. (Figure S4). The subset of residues painted blue represent the core union set that interact directly with the ligand in the PDZ1 co-crystal (2I1N), the PDZ2 co-crystal (2G2L), or the PDZ3 co-crystal (1BE9) by either van der Waals contacts of 3.9 Å or shorter or by hydrogen-bond lengths of 3.5 Å or shorter. (B) Ligand-binding residues are very highly conserved within a specific type of PDZ domain. Conservation of the 13 binding residues compared to the remaining 61 more distant residues for 16 types of PDZ domains from Homo, Drosophila, Nematostella and Amphimedon. These frequencies are also calculated across all those domains at once (column 1). Comparison of the conservation of binding residues versus non-binding residues; *, p<0.05; **, p<0.01; ***, p<0.001 (Probability associated with a Student's two-sample unequal variance t-Test).
Figure 2 (A) Sponge PDZ3—CRIPT Homology Model. The last five residues of the CRIPT protein (yellow) interact with PDZ3 residues (blue and orange) by making van der Waals contacts, hydrogen bonds, or electrostatic interactions of greater than 0.1 kcal/mol in magnitude in any of the PDZ3 homology models. (Figure S4). The subset of residues painted blue represent the core union set that interact directly with the ligand in the PDZ1 co-crystal (2I1N), the PDZ2 co-crystal (2G2L), or the PDZ3 co-crystal (1BE9) by either van der Waals contacts of 3.9 Å or shorter or by hydrogen-bond lengths of 3.5 Å or shorter. (B) Ligand-binding residues are very highly conserved within a specific type of PDZ domain. Conservation of the 13 binding residues compared to the remaining 61 more distant residues for 16 types of PDZ domains from Homo, Drosophila, Nematostella and Amphimedon. These frequencies are also calculated across all those domains at once (column 1). Comparison of the conservation of binding residues versus non-binding residues; *, p<0.05; **, p<0.01; ***, p<0.001 (Probability associated with a Student's two-sample unequal variance t-Test).CC BY · PubMed Central
Figure 3 Expression of Post-Synaptic Orthologs in Amphimedon Larvae. DLG, GKAP, GRIP, HOMER and CRIPT. All five genes (listed across the top) are expressed in the flask cells of Amphimedon larvae. (A–E) Sections of whole mount in situ hybridized larvae, with the posterior pole to the top. OL, outer epithelial- like layer; SL, subepithelial (middle) layer; ICM, inner cell mass. (F–J) Magnification of OL and SLs, with flask cells distributed in OL. (K–O) Scale bars: a–e, 100 µm; f–j, 50 µm; k–o, 10 µm.
Figure 3 Expression of Post-Synaptic Orthologs in Amphimedon Larvae. DLG, GKAP, GRIP, HOMER and CRIPT. All five genes (listed across the top) are expressed in the flask cells of Amphimedon larvae. (A–E) Sections of whole mount in situ hybridized larvae, with the posterior pole to the top. OL, outer epithelial- like layer; SL, subepithelial (middle) layer; ICM, inner cell mass. (F–J) Magnification of OL and SLs, with flask cells distributed in OL. (K–O) Scale bars: a–e, 100 µm; f–j, 50 µm; k–o, 10 µm.CC BY · PubMed Central

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Metadata

Authors
Sakarya, O., Armstrong, K. A., Adamska, M., Adamski, M., Wang, I.-F., Tidor, B., Degnan, B. M., Oakley, T. H., & Kosik, K. S.
Affiliations
  • University of California, Santa Barbara (US)
  • MIT Computer Science and Artificial Intelligence Laboratory (US)
  • The University of Queensland (AU)
Corresponding author
Kosik, Kenneth S.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2007-06-06
Volume
2
Issue
6
Pages
e506
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0000506
PMC
PMC1876816
OpenAlex
W2079236594
Cited by
291
References
52
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 13 · 2019: 15 · 2018: 8 · 2017: 16 · 2016: 21 · 2015: 28 · 2014: 20 · 2013: 12 · 2012: 18
FWCI
24.18
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • U.S. Department of Energy
  • Joint Genome Institute
Topics
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Marine Invertebrate Physiology and Ecology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
sponge genome, Amphimedon queenslandica, PDZ domain, protein interaction motifs, ionotropic glutamate receptors, Eumetazoa, protein complex formation
MeSH terms
Animals, Humans, Nerve Tissue Proteins, Porifera, Synapses, Genome, Evolution, Molecular

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