Characterization of the proteome, diseases and evolution of the human postsynaptic density
Open accessAbstract
We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases and were enriched in cognitive, affective and motor phenotypes underpinned by sets of genes. Strong protein sequence conservation in mammalian lineages, particularly in hub proteins, indicates conserved function and organization in primate and rodent models. The hPSD is an important structure for nervous system disease and behavior.
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ITSN1 and DPP6 are part of the postsynaptic density components in human neocortex.
“ITSN1 and DPP6 are part of the postsynaptic density components in human neocortex.36”
From Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes (2019) · cites this paper as [36]
The composition of the PSD has recently been identified in humans by some of the present authors.
“The composition of the PSD has recently been identified in humans by some of the present authors,34”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [34]
DLG family MAGUKs are components of postsynaptic signalling complexes embedded within the PSD.
“The DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs), which were hit by multiple case de novo CNVs, are components of postsynaptic signalling complexes that are embedded within the larger group of over 1000 proteins that make up the PSD.34”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [34]
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 [191]
The authors observed case-control enrichment of dURVs among genes encoding interactors with PSD-95 (OR=1.52; 95% CI 1.21-1.90; P=0.0017) and ARC and NMDAR (OR=1.55; 95% CI=1.21-1.98; P=0.0028).
“We observed case-control enrichment of dURVs among genes thus defined as encoding interactors with PSD-95 (OR=1.52; 95% CI 1.21–1.90; P = 0.0017), ARC and N-methyl-D-aspartate receptors (NMDAR)35 (OR=1.55; 95% CI=1.21–1.98; P = 0.0028) (Fig. 2).”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [35]
The human excitatory postsynaptic density contains 740 genes.
“we examined the 740 genes identified in the human excitatory postsynaptic density (PSD12)”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [12]
The 569 unique proteins among the 579 proteins (10 had isoforms) were categorized into presynaptic (N = 159), postsynaptic (N = 150), both (N = 20), or other (N = 240).
“The 569 unique proteins among these 579 proteins (10 had isoforms) were categorized into presynaptic (N = 159), postsynaptic (N = 150), both (present in both presynaptic and postsynaptic density; N = 20), or other (N = 240) using Boyken et. al. presynaptic list16 and Bayes et. al. postsynaptic density list17 (Supplementary Data 3).”
From Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age (2019) · cites this paper as [17]
Synaptic proteins, including glutamate receptors, are rarely subject to extensive structural changes from one species to the next.
“Given their importance for the normal functioning of the organism, synaptic proteins, including glutamate receptors, are rarely subject to extensive structural changes from one species to the next (Bayés et al., 2011;Ryan and Grant, 2009;Goto et al., 2009;Wada et al., 2004).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Bayés et al., 2011
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- Authors
- Bayés, À., van de Lagemaat, L. N., Collins, M. O., Croning, M. D. R., Whittle, I. R., Choudhary, J. S., & Grant, S. G. N.
- Affiliations
- Wellcome Sanger Institute (GB)
- University of Edinburgh (GB)
- Corresponding author
- Grant, Seth G N
- Venue
- Nature Neuroscience
- Published
- 2010-12-19
- Volume
- 14
- Issue
- 1
- Pages
- 19-21
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3040565
- OpenAlex
- W1967232661
- Cited by
- 499
- References
- 14
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 21 · 2023: 21 · 2022: 26 · 2021: 28 · 2020: 37 · 2019: 44 · 2018: 47 · 2017: 43 · 2016: 35 · 2015: 33 · 2014: 42 · 2013: 28 · 2012: 39
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Wellcome Trust (066717, 89569, 077155)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- postsynaptic density, human neocortex, proteome, neurological disorders, mental illness, cognitive phenotypes, motor phenotype, protein sequence conservation, hub proteins
- MeSH terms
- Animals, Central Nervous System Diseases, Pan troglodytes, Humans, Macaca, Mutation, Nerve Tissue Proteins, Species Specificity, Evolution, Molecular, Neocortex, Proteome, Mice, Rats, Post-Synaptic Density
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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