Synapse diversity and synaptome architecture in human genetic disorders
Open accessAbstract
Over 130 brain diseases are caused by mutations that disrupt genes encoding the proteome of excitatory synapses. These include neurological and psychiatric disorders with early and late onset such as autism, schizophrenia and depression and many other rarer conditions. The proteome of synapses is highly complex with over 1000 conserved proteins which are differentially expressed generating a vast, potentially unlimited, number of synapse types. The diversity of synapses and their location in the brain are described by the synaptome. A recent study has mapped the synaptome across the mouse brain, revealing that synapse diversity is distributed into an anatomical architecture observed at scales from individual dendrites to the whole systems level. The synaptome architecture is built from the hierarchical expression and assembly of proteins into complexes and supercomplexes which are distributed into different synapses. Mutations in synapse proteins change the synaptome architecture leading to behavioral phenotypes. Mutations in the mechanisms regulating the hierarchical assembly of the synaptome, including transcription and proteostasis, may also change synapse diversity and synaptome architecture. The logic of synaptome hierarchical assembly provides a mechanistic framework that explains how diverse genetic disorders can converge on synapses in different brain circuits to produce behavioral phenotypes.
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The identification of large multiprotein complexes associated with NMDA receptors and MAGUK proteins expanded the known synaptic proteome by tenfold.
“The identification of large multiprotein complexes, such as those associated with N-methyl-D-aspartate (NMDA) receptors and membrane-associated guanylate kinase (MAGUK) proteins, expanded the known synaptic proteome by tenfold, opening new avenues for research into synaptic organization and disease [10].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [10]
Disruptions in the hierarchical assembly of proteins within the "synaptome architecture" can lead to widespread behavioral phenotypes.
“Disruptions in the hierarchical assembly of proteins within the “synaptome architecture” can lead to widespread behavioral phenotypes, highlighting the PSD as a critical target for understanding and treating complex neurological and psychiatric conditions [10].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [10]
The synaptome is built from the hierarchical expression and assembly of proteins into complexes and supercomplexes.
“The “synaptome,” which describes the diversity of synapses and their anatomical distribution, is built from the hierarchical expression and assembly of proteins into complexes and supercomplexes [4,10].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [10]
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Global landscape of protein complexes in the yeast Saccharomyces cerevisiae
Krogan, N. J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., Li, J., Pu, S., Datta, N., Tikuisis, A., et al. (2006) · Nature · doi:10.1038/nature04670 · Cited by 2,915 · cited 1× · see citing works
“Eukaryotic proteins are rarely found as monomers, and almost all are assembled with binding partners into multiprotein complexes (17,18).”
BackgroundProteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,544 · cited 1× · see citing works
“Eukaryotic proteins are rarely found as monomers, and almost all are assembled with binding partners into multiprotein complexes (17,18).”
BackgroundDe novo mutations in schizophrenia implicate synaptic networks
Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., et al. (2014) · Nature · doi:10.1038/nature12929 · Cited by 1,617 · see citing works
Self-citationA polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385 · see citing works
Self-citationProteomic analysis of NMDA receptor–adhesion protein signaling complexes
Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., & Grant, S. G. N. (2000) · Nature Neuroscience · doi:10.1038/76615 · Cited by 1,194 · cited 3× · see citing works
“This revealed that 77 proteins assembled into large multiprotein complexes, and this increased the number of known proteins by 10-fold (1,2).”
BackgroundInfluentialSelf-citationMigaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G. M., Morrison, J. H., et al. (1998) · Nature · doi:10.1038/24790 · Cited by 1,160 · cited 1× · see citing works
“Disruption of these signaling complexes, as evidenced by mutations in the scaffold protein PSD95 and its interacting proteins, causes behavioral abnormalities and interferes with the ability of synapses to respond to patterns of nerve cell activity (12,13,20,21).”
BackgroundSelf-citationKirov, G., Pocklington, A. J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.154 · Cited by 844 · see citing works
Self-citationCharacterization of the proteome, diseases and evolution of the human postsynaptic density
Bayés, À., van de Lagemaat, L. N., Collins, M. O., Croning, M. D. R., Whittle, I. R., Choudhary, J. S., & Grant, S. G. N. (2011) · Nature Neuroscience · doi:10.1038/nn.2719 · Cited by 499 · see citing works
Self-citationThe CaM kinase II hypothesis for the storage of synaptic memory
Lisman, J. E. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90014-0 · Cited by 499 · cited 1× · see citing works
“John Lisman(11) proposed that a mere handful of proteins (the subunits of three protein complexes: the NMDA and α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the serine-threonine kinase CamKII) in mammalian excitatory synapses would be necessary and sufficient for synaptic transmission and t…”
BackgroundPeng, J., Kim, M. J., Cheng, D., Duong, D. M., Gygi, S. P., & Sheng, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400103200 · Cited by 473 · see citing works
Collins, M., Husi, H., Yu, L., Brandon, J. M., Anderson, C. N. G., Blackstock, W., Choudhary, J., & Grant, S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03507.x · Cited by 448 · see citing works
Self-citationKomiyama, N. H., Watabe, A. M., Carlisle, H. J., Porter, K., Charlesworth, P., Monti, J., Strathdee, D. J. C., O'Carroll, C. M., Martin, S. J., Morris, R. G. M., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09721.2002 · Cited by 382 · cited 1× · see citing works
“Disruption of these signaling complexes, as evidenced by mutations in the scaffold protein PSD95 and its interacting proteins, causes behavioral abnormalities and interferes with the ability of synapses to respond to patterns of nerve cell activity (12,13,20,21).”
BackgroundSelf-citationProteomic Analysis of in Vivo Phosphorylated Synaptic Proteins
Collins, M. O., Yu, L., Coba, M. P., Husi, H., Campuzano, I., Blackstock, W. P., Choudhary, J. S., & Grant, S. G. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411220200 · Cited by 320 · see citing works
Self-citationFernández, E., Collins, M. O., Uren, R. T., Kopanitsa, M. V., Komiyama, N. H., Croning, M. D. R., Zografos, L., Armstrong, J. D., Choudhary, J. S., & Grant, S. G. N. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.27 · Cited by 275 · see citing works
Self-citationArchitecture of the Mouse Brain Synaptome
Zhu, F., Cizeron, M., Qiu, Z., Benavides‐Piccione, R., Kopanitsa, M. V., Skene, N., Koniaris, B., DeFelipe, J., Fransén, E. A., Komiyama, N. H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.007 · Cited by 272 · see citing works
Self-citationBayés, À., Collins, M. O., Croning, M. D. R., van de Lagemaat, L. N., Choudhary, J. S., & Grant, S. G. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046683 · Cited by 216 · see citing works
Self-citationDeep molecular diversity of mammalian synapses: why it matters and how to measure it
O'Rourke, N. A., Weiler, N. C., Micheva, K. D., & Smith, S. J. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3170 · Cited by 210 · cited 2× · see citing works
“First, there is a need to develop a conceptual framework and nomenclature to describe the diversity (28,30).”
BackgroundEvolutionary expansion and anatomical specialization of synapse proteome complexity
Emes, R. D., Pocklington, A., Anderson, C. N. G., Bayés, À., Collins, M., Vickers, C., Croning, M., Malik, B., Choudhary, J., Armstrong, J., et al. (2008) · Nature Neuroscience · doi:10.1038/nn.2135 · Cited by 202 · see citing works
Self-citationTargeted Combinatorial Alternative Splicing Generates Brain Region-Specific Repertoires of Neurexins
Schreiner, D., Nguyen, T.-M., Russo, G., Heber, S., Patrignani, A., Ahrné, E., & Scheiffele, P. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.011 · Cited by 183 · cited 2× · see citing works
“For example, alternatively spliced neurexin isoforms can potentially produce many thousands of different proteins from a single gene, and triggering of neurotransmitter receptors can induce posttranslational changes in hundreds of proteins (14,27).”
BackgroundFrank, R., Komiyama, N. H., Ryan, T. J., Zhu, F., O’Dell, T. J., & Grant, S. G. N. (2016) · Nature Communications · doi:10.1038/ncomms11264 · Cited by 169 · cited 1× · see citing works
“A survey of over 60 synaptic proteins found that all were assembled into a hierarchy of multiprotein complexes and supercomplexes (complexes of complexes) (19).”
BackgroundSelf-citationFrom the Connectome to the Synaptome: An Epic Love Story
DeFelipe, J. (2010) · Science · doi:10.1126/science.1193378 · Cited by 168 · cited 1× · see citing works
“As a step toward the first issue, the term synaptome was coined to describe the set of synapses in the brain (31,32).”
BackgroundHusi, H., & Grant, S. G. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00248.x · Cited by 134 · see citing works
Self-citationPocklington, A. J., Cumiskey, M. A., Armstrong, J. D., & Grant, S. G. N. (2006) · Molecular Systems Biology · doi:10.1038/msb4100041 · Cited by 130 · see citing works
Self-citationNeurotransmitters Drive Combinatorial Multistate Postsynaptic Density Networks
Coba, M. P., Pocklington, A. J., Collins, M. O., Kopanitsa, M. V., Uren, R. T., Swamy, S., Croning, M. D. R., Choudhary, J. S., & Grant, S. G. N. (2009) · Science Signaling · doi:10.1126/scisignal.2000102 · Cited by 129 · see citing works
Self-citationSupramolecular organization of NMDA receptors and the postsynaptic density
Frank, R., & Grant, S. G. N. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.05.019 · Cited by 119 · see citing works
Self-citationEvolution of complexity in the zebrafish synapse proteome
Bayés, À., Collins, M. O., Reig‐Viader, R., Gou, G., Goulding, D., Izquierdo, A., Choudhary, J. S., Emes, R. D., & Grant, S. G. N. (2017) · Nature Communications · doi:10.1038/ncomms14613 · Cited by 115 · see citing works
Self-citationDistler, U., Schmeißer, M. J., Pelosi, A., Reim, D., Kuharev, J., Weiczner, R., Baumgart, J., Boeckers, T. M., Nitsch, R., Vogt, J., et al. (2014) · PROTEOMICS · doi:10.1002/pmic.201300520 · Cited by 104 · see citing works
Fernández, E., Collins, M. O., Frank, R., Zhu, F., Kopanitsa, M. V., Nithianantharajah, J., Lemprière, S. A., Fricker, D. G., Elsegood, K. A., McLaughlin, C. L., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.045 · Cited by 88 · see citing works
Self-citationProteomic analysis of postsynaptic proteins in regions of the human neocortex
Roy, M. M., Sorokina, O., Skene, N., Simonnet, C., Mazzo, F., Zwart, R., Sher, E., Smith, C., Armstrong, J. D., & Grant, S. G. N. (2017) · Nature Neuroscience · doi:10.1038/s41593-017-0025-9 · Cited by 82 · cited 1× · see citing works
“functional brain imaging (Positron Emission Tomography (PET) and fMRI) (39) and that the mouse synaptome network topology”
BackgroundSelf-citationPerturbed proteostasis in autism spectrum disorders
Louros, S. R., & Osterweil, E. K. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13723 · Cited by 79 · cited 1× · see citing works
“It is likely that synaptome pathology will be a common feature of autism, as many of the susceptibility genes encode synapse proteins and regulators of proteostasis (37).”
BackgroundFrank, R., Zhu, F., Komiyama, N. H., & Grant, S. G. N. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14056 · Cited by 60 · see citing works
Self-citationA genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
Skene, N., Roy, M. M., & Grant, S. G. N. (2017) · eLife · doi:10.7554/elife.17915 · Cited by 51 · cited 1× · see citing works
“One of the most puzzling features of some germline mutations is that their phenotypes manifest at late ages and in particular regions of the brain despite the gene being widely and continuously expressed (33).”
BackgroundSelf-citationFmr1 KO and Fenobam Treatment Differentially Impact Distinct Synapse Populations of Mouse Neocortex
Wang, G. X., Smith, S. J., & Mourrain, P. (2014) · Neuron · doi:10.1016/j.neuron.2014.11.016 · Cited by 35 · cited 1× · see citing works
“understanding how basic cell biological mechanisms control the synaptome architecture of the whole brain, focused studies have shown that mice carrying a mutation in Fmr1, an RNA binding protein involved with autism, cause changes in distinct subpopulations of synapses in mouse neocortex (36).”
BackgroundToward a molecular catalogue of synapses
Grant, S. G. N. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.003 · Cited by 29 · cited 1× · see citing works
“First, there is a need to develop a conceptual framework and nomenclature to describe the diversity (28,30).”
BackgroundSelf-citationThe Synaptomic Theory of Behavior and Brain Disease.Preprint
Grant, S. (2019) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2018.83.037887 · Cited by 23 · cited 1× · see citing works
“We have developed a theory called the Synaptomic Theory that explains how synapse diversity and synaptome maps can store information (innate and learned behaviors) that can be “recalled” by patterns of nerve cell activity (38).”
BackgroundSelf-citationSynaptic Plasticity In Vitro and In Silico: Insights into an Intracellular Signaling Maze
Ajay, S. M., & Bhalla, U. S. (2006) · Physiology · doi:10.1152/physiol.00009.2006 · Cited by 13 · see citing works
Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice
Zhu, F., Collins, M., Harmse, J., Choudhary, J., Grant, S., & Komiyama, N. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14597 · Cited by 10 · see citing works
Self-citationKopanitsa, M., van de Lagemaat, L. N., Afinowi, N. O., Strathdee, D., Strathdee, K., Fricker, D. G., Tuck, E. J., Elsegood, K., Croning, M., Komiyama, N., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/500447 · Cited by 10 · see citing works
Self-citationCell-type specific visualization and biochemical isolation of endogenous synaptic proteins in mice
Zhu, F., Collins, M., Harmse, J., Choudhary, J., Grant, S., & Komiyama, N. (2018) · bioRxiv · doi:10.1101/363614 · Cited by 9 · cited 1×
“Synapse diversity is now beginning to be studied with modern molecular techniques (28, 29) but remains poorly understood for at least two reasons.”
BackgroundSelf-citationSynaptic combinatorial molecular mechanisms generate repertoires of innate and learned behaviorPreprint
Komiyama, N. H., van de Lagemaat, L. N., Stanford, L. E., Pettit, C. M., Strathdee, D., Strathdee, K. E., Fricker, D. G., Tuck, E. J., Elsegood, K. A., Ryan, T. J., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/500389 · Cited by 8 · see citing works
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The synapse in traumatic brain injury
Jamjoom, A. A. B., Rhodes, J. K. J., Andrews, P., & Grant, S. G. N. (2020) · Brain · doi:10.1093/brain/awaa321 · Cited by 243 · see citing works
“…than previously anticipated; each brain region has a particular signature of synapse composition, and the synapse proteomes of brain regions differ from one another (Micheva et al., 2010; O’Rourke et al., 2012; Broadhead et al., 2016; Grant, 2018, 2019; Zhu et al., 2018; Cizeron et al., 2020).”
BackgroundSelf-citationThe proteomic landscape of synaptic diversity across brain regions and cell typesPreprint
van Oostrum, M., Blok, T., Giandomenico, S. L., Dieck, S. T., Tushev, G., Fürst, N., Langer, J., & Schuman, E. (2023) · bioRxiv · doi:10.1101/2023.01.27.525780 · Cited by 110 · see citing works
DLG4-related synaptopathy: a new rare brain disorder
Rodríguez‐Palmero, A., Boerrigter, M. M., Gómez‐Andrés, D., Aldinger, K. A., Marcos‐Alcalde, Í., Popp, B., Everman, D. B., Lovgren, A. K., Arpin, S., Bahrambeigi, V., et al. (2021) · Genetics in Medicine · doi:10.1038/s41436-020-01075-9 · Cited by 64 · see citing works
Synapse vulnerability and resilience underlying Alzheimer’s disease
Taddei, R. N., & Duff, K. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105557 · Cited by 46 · see citing works
“Genome-wide association studies have revealed additional genetic resilience variants, including bile acid metabolism-associated pathways, variants on chromosomes 1, 5, 13, and 18, 107 and protective effects of BDNF and DLGAP.”
Enriched environment-induced neuroplasticity in ischemic stroke and its underlying mechanisms
Han, P.-P., Han, Y., Shen, X.-Y., Gao, Z.-K., & Bi, X. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1210361 · Cited by 45 · see citing works
“The presynaptic membrane releases neurotransmitters, which travel across the synaptic gap to the postsynaptic membrane, triggering a change in potential and transmitting the information (Grant, 2019).”
BackgroundA single-synapse resolution survey of PSD95-positive synapses in twenty human brain regions
Curran, O. E., Qiu, Z., Smith, C., & Grant, S. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14846 · Cited by 34 · see citing works
“Mutations in Dlg3 and Dlg2 , which cause intellectual disability and schizophrenia in humans, respectively, caused a change in the PSD95 synap-tome architecture, suggesting that synaptic diseases manifest with altered spatial distribution of excitatory synapse types (Grant, 2019; Zhu et al., 2018).”
BackgroundInfluentialSelf-citationDistler, U., Schumann, S., Kesseler, H.-G., Pielot, R., Smalla, K., Sielaff, M., Schmeißer, M. J., & Tenzer, S. (2020) · Cells · doi:10.3390/cells9020313 · Cited by 35 · see citing works
Electrical synaptic transmission requires a postsynaptic scaffolding protein
Lasseigne, A. M., Echeverry, F. A., Ijaz, S., Michel, J. J. C., Martin, E. A., Marsh, A. J., Trujillo, E., Marsden, K. C., Pereda, A. E., & Miller, A. C. (2021) · eLife · doi:10.7554/elife.66898 · Cited by 42 · see citing works
The Synapse Diversity Dilemma: Molecular Heterogeneity Confounds Studies of Synapse Function
Grant, S., & Fransen, E. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.590403 · Cited by 29 · see citing works
“In addition to this mechanism, we have previously described “synaptome reprograming” in mice carrying gene mutations (Zhu et al., 2018; Grant, 2019).”
BackgroundSelf-citationSelective vulnerability of tripartite synapses in amyotrophic lateral sclerosis
Broadhead, M. J., Bonthron, C., Waddington, J., Smith, W. V., Lopez, M. F., Burley, S., Valli, J., Zhu, F., Komiyama, N. H., Smith, C., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02412-9 · Cited by 39 · see citing works
Self-citationRole of calcium/calmodulin-dependent kinase 2 in neurodevelopmental disorders
Onori, M. P., & van Woerden, G. M. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.03.014 · Cited by 29 · see citing works
“Despite differences in molecular composition of the PSD between different neuronal types and brain regions (Bayés et al., 2011, 2012; Grant, 2019; Zhu et al., 2018a,b), some key elements such as PSD-95, Shank, Homer and CAMK2 constitute the main scaffold around which the postsynaptic compartment…”
Integrating and interpreting brain maps
Hansen, J. Y., & Mišić, B. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.06.003 · Cited by 20 · see citing works
“Whole-brain 3D brain maps of neurotransmitter receptor autoradiographs [26], proteomic synaptome structure [22,122], and micron-resolution cellular architecture [14] are all imminent.”
Dissecting shared genetic architecture between depression and body mass index
Zhang, H., Zheng, R., Yu, B., Yu, Y., Luo, X., Yin, S., Zheng, Y., Shi, J., & Ai, S. (2024) · BMC Medicine · doi:10.1186/s12916-024-03681-9 · Cited by 23 · see citing works
“Consistent with our findings, many proteins regulated by genes in conserved regions, such as REDD1 , DOC , and the proteome of synapses, are associated with depression, obesity, and metabolic risk [50, 51].”
BackgroundProteomic insights into synaptic signaling in the brain: the past, present and future
Xu, Y., Song, X., Wang, D., Wang, Y., Li, P., & Li, J. (2021) · Molecular Brain · doi:10.1186/s13041-021-00750-5 · Cited by 50 · see citing works
Molecular signatures from multi‐omics of autism spectrum disorders and schizophrenia
Nomura, J., Mardo, M., & Takumi, T. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15514 · Cited by 21 · see citing works
“The molecular hierarchy of synaptic protein complexes may also be dysregulated by genetic mutations (Grant, 2019).”
BackgroundChristensen, N. R., Pedersen, C. P., Sereikaité, V., Pedersen, J. N., Vistrup-Parry, M., Sørensen, A. T., Otzen, D. E., Teilum, K., Madsen, K. L., & Strømgaard, K. (2022) · iScience · doi:10.1016/j.isci.2022.103808 · Cited by 14 · see citing works
Halewa, J., Marouillat, S., Dixneuf, M., Thepault, R., Ung, D., Chatron, N., Gerard, B., Ghoumid, J., Lesca, G., Till, M., et al. (2021) · Human Mutation · doi:10.1002/humu.24208 · Cited by 13 · see citing works
“The p.Pro32Arg mutation was found in a patient with ID and inherited from his mother; the p.(Pro32Leu) was identified in a patient with NDD and was also present in an uncle T A B L E 1 C lin ic al ,m o le cu la r, in si lic o p at h o ge n ic it y p re d ic ti o n d et ai ls ,a n d fu n ct io n al an al ys es o n th e…”
BackgroundInfluentialYamamoto, K., Kuriu, T., Matsumura, K., Nagayasu, K., Tsurusaki, Y., Miyake, N., Yamamori, H., Yasuda, Y., Fujimoto, M., Fujiwara, M., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01676-1 · Cited by 22 · see citing works
Moradi, K., Aldarraji, Z., Luthra, M., Madison, G. P., & Ascoli, G. A. (2022) · Communications Biology · doi:10.1038/s42003-022-03329-5 · Cited by 14 · see citing works
“Notes 6 – 7 for future directions).”
BackgroundSperanza, L., Filiz, K. D., Goebel, S., Perrone‐Capano, C., Pulcrano, S., Volpicelli, F., & Francesconi, A. (2022) · Biomedicines · doi:10.3390/biomedicines10112692 · Cited by 10 · see citing works
Jospin, M., Bonneau, B., Lainé, V., & Bessereau, J. (2022) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2113545119 · Cited by 8 · see citing works
Melišková, V., Havránek, T., Bačová, Z., & Bakoš, J. (2021) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2004106 · Cited by 7 · see citing works
Molecular Physiology of the Neuronal Synapse
Ramírez-Expósito, M. J., Cueto-Ureña, C., & Martínez-Martos, J. M. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48010088 · Cited by 6 · see citing works
“Disrup-tions in the hierarchical assembly of proteins within the “synaptome architecture” can lead to widespread behavioral phenotypes, highlighting the PSD as a critical target for understanding and treating complex neurological and psychiatric conditions [10].”
InfluentialVerpoort, B., Amado, L., Vandensteen, J., Leysen, E., Dascenco, D., Vandenbempt, J., Lemmens, I. H., Wauman, J., Vennekens, K. M., Escamilla‐Ayala, A., et al. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.04.025 · Cited by 8 · see citing works
Crystallographic Studies of PDZ Domain–Peptide Interactions of the Scribble Polarity Module
Maddumage, J. C., Stewart, B. Z., Humbert, P. O., & Kvansakul, M. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1166-1_7 · Cited by 7 · see citing works
Developing a Toolbox of Antibodies Validated for Array Tomography-Based Imaging of Brain Synapses
Micheva, K. D., Gong, B., Collman, F., Weinberg, R., Smith, S. J., Trimmer, J., & Murray, K. (2023) · bioRxiv · doi:10.1101/2023.06.28.546920 · Cited by 5
“This is especially problematic for synapse-associated proteins, which are extensively regulated by posttranslational modifications and participate in complex and densely packed networks of interacting proteins (Grant, 2006; Zhu et al., 2018; Grant, 2019; Helm et al., 2021).”
BackgroundDiab, A. M., Qi, J., Shahin, I., Milligan, C., & Fawcett, J. P. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.09.026 · Cited by 8 · see citing works
Acupuncture intervening depressive disorder: research progress in its neurobiological mechanism
Li, P., Xiao, M., Ma, X., Yan, X., & Ma, C.-B. (2023) · Journal of Acupuncture and Tuina Science · doi:10.1007/s11726-023-1381-5 · Cited by 4 · see citing works
Human mutations in SLITRK3 implicated in GABAergic synapse development in mice
Efthymiou, S., Han, W., Ilyas, M., Li, J., Yu, Y., Scala, M., Malintan, N. T., Vavouraki, N., Mankad, K., Maroofian, R., et al. (2022) · bioRxiv · doi:10.3389/fnmol.2024.1222935 · Cited by 4 · see citing works
“Given that the synaptopathies are defined as brain disorders associated with synaptic dysfunction (Grant, 2019) and that the individuals presented in this study have clinical features overlapping those observed in individuals with synaptopathies (cognitive disorders such as intellectual disability,…”
BackgroundWan, L. P., Li, Y., Zhao, S., Zhao, S., Song, N., Yuan, K., Yang, C., Ding, Y., Mao, B., Sheng, N., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2426375122 · Cited by 3 · see citing works
Molecular mechanisms of the specialization of human synapses in the neocortex
Christopoulou, E., & Charrier, C. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102258 · Cited by 1 · see citing works
Electrical synapse structure requires distinct isoforms of a postsynaptic scaffold
Michel, J. J. C., Grivette, M. M. B., Harshfield, A. T., Huynh, L., Komons, A. P., Loomis, B., McKinnis, K., Miller, B. T., Nguyen, E. Q., Huang, T. W., et al. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1011045 · Cited by 4 · see citing works
Miski, M., Weber, Á., Fekete-Molnár, K., Keömley-Horváth, B. M., Csikász‐Nagy, A., & Gáspári, Z. (2024) · BMC Neuroscience · doi:10.1186/s12868-024-00880-1 · Cited by 4 · see citing works
“…of brain functions, including learning and memory [1, 2] There are a number of experimental observations indicating that the postsynaptic density (PSD), utilizing the same major constituent proteins, can be highly variable depending on the abundance of its individual protein components [3].”
BackgroundEagleson, K. L., & Levitt, P. R. (2023) · Developmental Neuroscience · doi:10.1159/000529981 · Cited by 4 · see citing works
Synapse types are spatially associated with regional hemodynamics in the mouse brain
Hansen, J. Y., Luppi, A. I., Qiu, Z., Gini, S., Fulcher, B., Gozzi, A., Grant, S. G. N., & Mišić, B. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003637 · Cited by 1 · see citing works
Self-citationRibeiro‐Constante, J., Romagosa, J., Oyarzábal, A., Rull, E. X. M., & García‐Cazorla, À. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.23.701319 · Cited by 1 · see citing works
“38,39 Developmental gene expression patterns shape common neurological symptoms Gene expression patterns during brain development play a crucial role in the manifestation of neurological symptoms associated with synaptic genes.”
Exploring Synaptic Pathways in Traumatic Brain Injury: A Cross-Phenotype Genomics Approach
Prapiadou, S., Mayerhofer, E., Georgakis, M. K., Kals, M., Radmanesh, F., Izzy, S., Richardson, S. T., Okonkwo, D. O., Puccio, A. M., Temkin, N. R., et al. (2024) · Journal of Neurotrauma · doi:10.1089/neu.2024.0153 · Cited by 2 · see citing works
“One such putative mechanism is the synaptome, de fi ned as a comprehensive description of each synapse, encompassing its characteristics, spatial distribution in the brain, constituent elements, and the structural and functional connections it exhibits 17 .”
Ma, R.-Y., & Han, K. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02720-4 · Cited by 1
Developing a Toolbox of Antibodies Validated for Array Tomography-Based Imaging of Brain Synapses
Micheva, K. D., Gong, B., Collman, F., Weinberg, R. J., Smith, S. J., Trimmer, J. S., & Murray, K. D. (2023) · eNeuro · doi:10.1523/eneuro.0290-23.2023 · Cited by 9 · see citing works
“This is especially problematic for synapse-associated proteins, which are extensively regulated by posttranslational modifications and participate in complex and densely packed networks of interacting proteins (Grant, 2006, 2019; Zhu et al., 2018; Helm et al., 2021).”
BackgroundStepwise molecular specification of excitatory synapse diversity on a target neuron
Paul, M. A., Sigoillot, S., Marti, L., Delagrange, M., Mailly, P., & Selimi, F. (2023) · bioRxiv · doi:10.1101/2023.01.03.521946 · Cited by 1
Kim, J., Chen, W., Chao, E. S., Chen, H.-M., & Xue, M.-S. (2021) · bioRxiv · doi:10.1101/2021.07.13.452234 · Cited by 1 · see citing works
Luo, S., Hou, Y., Zhang, Y., Ma, T., Shao, W., & Xiao, C. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-01007 · Cited by 1 · see citing works
Cipriano, G. L., Anchesi, I., Floramo, A., Argento, V., Spinelli, S., Astorino, M. F., Calabrò, M., & Artimagnella, O. (2026) · Cells · doi:10.3390/cells15161433
“…proteomic profiling, utilizing techniques such as Fluorescence-Activated Synaptosome Sorting (FASS), has isolated the proteomes of genetically defined synaptic populations, revealing that excitatory and inhibitory synapses harbor fundamentally distinct, mutually exclusive protein communities [10].”
Nagy-Kanta, E., Sánta, A., Kálmán, Z. E., Li, J. A., Permi, P., Gáspári, Z., & Péterfia, B. (2025) · Biomolecular NMR Assignments · doi:10.1007/s12104-025-10253-2
Data-driven synapse classification reveals a logic of glutamate receptor diversityPreprint
Micheva, K. D., Simhal, A. K., Schardt, J., Smith, S. J., Weinberg, R. J., & Owen, S. F. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.11.628056 · Cited by 1 · see citing works
Michel, J. J. C., Grivette, M. M. B., Harshfield, A. T., Huynh, L., Komons, A. P., Loomis, B., McKinnis, K., Miller, B. T., Nguyen, E. Q., Huang, T. W., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.27.497867
“At chemical synapses, hundreds of proteins are associated with the presynaptic active zone (AZ) and postsynaptic density (PSD) and regulate synaptic vesicle release and neurotransmitter localization, respectively (Ackermann et al., 2015; Grant, 2019; Patel et al., 2006; Siddiqui and Craig, 2011).”
BackgroundSperanza, L., Filiz, K. D., Goebel, S., Perrone-Capano, C., Pulcrano, S., Volpicelli, F., & Francesconi, A. (2022) · bioRxiv · doi:10.1101/2022.09.20.508741
Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex
Moradi, K., Aldarraji, Z., Luthra, M., Madison, G. P., & Ascoli, G. A. (2021) · doi:10.21203/rs.3.rs-585433/v1
Kalman, Z. E., & Gáspári, Z. (2021) · bioRxiv · doi:10.1101/2021.01.25.428072
“The importance of the PSD is further enhanced by the fact that perturbation of certain hub proteins in the network has already been associated with more than hundred genetic diseases [4].”
BackgroundThe human and mouse synaptome architecture of excitatory synapses show conserved featuresPreprint
Curran, O. E., Qiu, Z., Smith, C., & Grant, S. (2020) · bioRxiv · doi:10.1101/2020.01.17.910547
“Because high synapse diversity arises from the differential distribution of synaptic proteins and their cognate multiprotein complexes (Grant, 2018; Zhu et al., 2018a; Grant, 2019), it is likely that a detailed characterization of the synaptome of diverse molecular types of synapses in humans and mice will reveal spec…”
BackgroundInfluentialSelf-citation
- Authors
- Grant, S. G. N.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Grant, Seth G N
- ORCID
- Grant, Seth G N
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-07-26
- Volume
- 28
- Issue
- R2
- Pages
- R219-R225
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC6872429
- OpenAlex
- W2965893335
- Cited by
- 67
- References
- 39
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 13 · 2020: 7
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Human Molecular Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome (202932)
- European Research Council Advanced Grant SYNNOVATE (695568)
- Simons Initiative for the Developing Brain
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- excitatory synapses, synapse proteome, neurological disorders, mental illness, autism spectrum disorder, schizophrenia, depression, synapse assembly, proteostasis, transcription, behavioral phenotypes, mouse brain
- MeSH terms
- Disks Large Homolog 4 Protein, Aging, Animals, Autistic Disorder, Depression, Humans, Membrane Proteins, Schizophrenia, Synapses, Proteome, Mice, Guanylate Kinases
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