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Protein trafficking and synaptic demand configure complex and dynamic synaptome architectures of individual neurons

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Sorokina, Oksana, Bulovaite, Edita, Sorokin, Anatoly, Grant, Seth G. N., Armstrong, J. Douglas·2026·Scientific Reports
DOI 10.1038/s41598-026-40513-7PMC PMC13057022
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Abstract

Excitatory synapses are the most abundant synapse type in the brain. Being essential for behaviour and implicated in hundreds of brain disorders, these synapses exhibit striking structural and functional diversity. Synaptome mapping at single-synapse resolution reveals that synaptic protein diversity is spatially organised along the dendritic tree of individual neurons and varies with age and cell type. However, the cell biological mechanisms underlying the generation of these complex spatial synaptic patterns remain poorly understood. Potential mechanisms include somatic and dendritic protein synthesis, protein trafficking, and local regulatory mechanisms such as activity-dependent degradation. Here we developed computational models to test how combinations of these processes account for empirical synaptome data. We found that a combination of molecular transport mechanisms and local synaptic demand for proteins was sufficient to explain very complex profiles of synaptic protein distributions observed in young, mature and old mice and in different cell types. Our findings suggest the highly complex and dynamic synaptome architecture of the brain is an emergent property of a minimal set of cell biological processes. Our model sets the stage for simulations of brain tissue incorporating molecularly diverse neuronal and synaptic types in a synaptome and connectome architecture.

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  • The lifetimes of brain proteins vary widely.

    “Moreover, the lifetimes of brain proteins vary widely [22][23][24]”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [23]

    The Introduction (page unavailable) says that synapse-protein turnover differs between synapses, and the Results section “PSD95 protein half-life varies with age” reports modeled PSD95 half-lives of 1.54 days in juvenile mice versus 4.3 days in mature mice. This supports variation in a brain protein’s lifetime, but the paper’s reported analysis focuses on PSD95 rather than establishing how widely lifetimes vary across brain proteins generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • A combination of molecular transport mechanisms and local synaptic demand for proteins was sufficient to account for complex profiles of synaptic protein distributions in different cell types.

    “They argue that a combination of molecular transport mechanisms and local synaptic demand for proteins was sufficient to account for complex profiles of synaptic protein distributions in different cell types.”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [23]

  • Simple rules can generate the complexity of biological synaptic organization.

    “They suggest that simple rules can generate the complexity of biological synaptic organization.”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [23]

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Cited by

Sorted by citations

Authors
Sorokina, O., Bulovaite, E., Sorokin, A., Grant, S. G. N., & Armstrong, J. D.
Affiliations
  • University of Edinburgh (GB)
  • Okinawa Institute of Science and Technology Graduate University (JP)
  • Simons Initiative for the Developing Brain (GB)
  • Forschungszentrum Jülich (DE)
Corresponding author
Armstrong, J. Douglas
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2026-03-02
Volume
16
Issue
1
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-026-40513-7
PMC
PMC13057022
OpenAlex
W7133197733
Cited by
2
References
1
Citations by year
2026: 2
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/X009343/1)
  • European Research Council (885069 SYNAPTOME)
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 › Cell Biology › Cellular transport and secretion
Keywords
excitatory synapses, protein trafficking, dendritic transport, dendritic protein synthesis, computational modelling, dendritic trees, aging, neuronal cell types, connectome
MeSH terms
Animals, Brain, Computer Simulation, Dendrites, Models, Neurological, Neurons, Synapses, Protein Transport, Mice

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