ArticleProceedings of the National Academy of Sciences of the United States of America2020
Hidden proteome of synaptic vesicles in the mammalian brain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 112 citations in OpenAlex.
- Proteomic maps of synapses and synaptic vesicles across the central and enteric nervous systems.Communications biology · 2026Article
- A computational theory of short-term synaptic plasticity: synapses learn to tell time.Research square · 2026Article
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- Lipofuscin accumulation in aging and CLN1 is associated with deficient de-S-acylation, lyso-mitochondrial dysfunction, and lipid dyshomeostasis.Acta neuropathologica · 2026Article
- APOE is a presynaptic protein that accumulates with age and modulates neurotransmitter release.bioRxiv : the preprint server for biology · 2026Article
- Deficient de-S-acylation in aging and CLN1 contributes to lyso-mitochondrial dysfunction, lipid dyshomeostasis, and resultant lipofuscin biogenesis.Research square · 2026Article
- Rab24 protein levels show dynamic changes in mouse tissues and human cancers.Cell and tissue research · 2026Article
- Proteomic Characterization of Spinal Cord Myelin in the Mouse.ASN neuro · 2026Article
- The Golgi apparatus: adaptations to neuronal shape and functions.The EMBO journal · 2026Review
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The synaptic vesicle cluster as a controller of pre- and postsynaptic structure and function.The Journal of physiology · 2025Review
- Biogenesis and reformation of synaptic vesicles.The Journal of physiology · 2025Review
- Proteomics-based receptor-ligand matching enhances differentiation maturity of human-stem-cell-derived neurons.Stem cell reports · 2025Article
- An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution.Nature communications · 2025Article
- An Open-Science Computational Model of Organelle Acidification to Integrate Putative Mechanisms of Synaptic Vesicle Acidification and Filling.Neurochemical research · 2025Article
- Emergent glutamate & dopamine dysfunction in VPS35NPJ Parkinson's disease · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading.Science advances · 2025Article
- Synapsin Condensation is Governed by Sequence-Encoded Molecular Grammars.Journal of molecular biology · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current proteomic studies clarified canonical synaptic proteins that are common to many types of synapses. However, proteins of diversified functions in a subset of synapses are largely hidden because of their low abundance or structural similarities to abundant proteins. To overcome this limitation, we have developed an "ultra-definition" (UD) subcellular proteomic workflow. Using purified synaptic vesicle (SV) fraction from rat brain, we identified 1,466 proteins, three times more than reported previously. This refined proteome includes all canonical SV proteins, as well as numerous proteins of low abundance, many of which were hitherto undetected. Comparison of UD quantifications between SV and synaptosomal fractions has enabled us to distinguish SV-resident proteins from potential SV-visitor proteins. We found 134 SV residents, of which 86 are present in an average copy number per SV of less than one, including vesicular transporters of nonubiquitous neurotransmitters in the brain. We provide a fully annotated resource of all categorized SV-resident and potential SV-visitor proteins, which can be utilized to drive novel functional studies, as we characterized here Aak1 as a regulator of synaptic transmission. Moreover, proteins in the SV fraction are associated with more than 200 distinct brain diseases. Remarkably, a majority of these proteins was found in the low-abundance proteome range, highlighting its pathological significance. Our deep SV proteome will provide a fundamental resource for a variety of future investigations on the function of synapses in health and disease.
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