Comparative Study of Human and Mouse Postsynaptic Proteomes Finds High Compositional Conservation and Abundance Differences for Key Synaptic Proteins
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Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities. The mouse postsynaptic density comprised 1556 proteins and the human one 1461. A large compositional overlap was observed; more than 70% of human postsynaptic density proteins were also observed in the mouse postsynaptic density. Quantitative analysis of postsynaptic density components in both species indicates a broadly similar profile of abundance but also shows that there is higher abundance variation between species than within species. Well known components of this synaptic structure are generally more abundant in the mouse postsynaptic density. Significant inter-species abundance differences exist in some families of key postsynaptic density proteins including glutamatergic neurotransmitter receptors and adaptor proteins. Furthermore, we have identified a closely interacting set of molecules enriched in the human postsynaptic density that could be involved in dendrite and spine structural plasticity. Understanding synapse proteome diversity within and between species will be important to further our understanding of brain complexity and disease.
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The postsynaptic density has been extensively characterized at the protein level in humans and mice, showing key areas of overlap and divergence.
“A particularly salient example is the synaptic signalling apparatus, more specifically the postsynaptic density (PSD), which has been extensively characterized at the protein level in humans and mice, showing key areas of overlap and divergence191,192.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [192]
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- Authors
- Bayés, À., Collins, M. O., Croning, M. D. R., van de Lagemaat, L. N., Choudhary, J. S., & Grant, S. G. N.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Bayés, Àlex
- Grant, Seth G. N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-10-05
- Volume
- 7
- Issue
- 10
- Pages
- e46683
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3465276
- OpenAlex
- W2093855178
- Cited by
- 216
- References
- 43
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 23 · 2023: 13 · 2022: 12 · 2021: 15 · 2020: 29 · 2019: 21 · 2018: 20 · 2017: 20 · 2016: 14 · 2015: 13 · 2014: 9 · 2013: 2 · 2012: 1
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (241498, 242167)
- European Commission (221540, 241498, 242167)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- postsynaptic density, synapse proteome, human-mouse comparison, protein abundance, excitatory synapses, glutamate receptors, dendritic spine plasticity, mammalian brain evolution, cortical synapses
- MeSH terms
- Animals, Centrifugation, Density Gradient, Cerebral Cortex, Chromatography, Gel, Female, Humans, Male, Nerve Tissue Proteins, Species Specificity, Synapses, Proteome, Mice, Tandem Mass Spectrometry, Mice, 129 Strain, Post-Synaptic Density, Protein Interaction Maps
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