ArticleThe EMBO journal2023
Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Transcriptional Profiling of Botulinum Neurotoxin Type A-Related Molecular Components in Primary Human Schwann Cells.Toxins · 2026Article
- Cryo-EM Structure Guided Engineering of Botulinum Neurotoxin A With Advanced Receptor Binding Affinity and Therapeutical Benefits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A versatile nanobody platform for live and super-resolution imaging of synaptic vesicle dynamics and plasticity in rodent and human neurons.Journal of nanobiotechnology · 2026Article
- Review
- From Gut to Systemic Circulation: Molecular Strategies of Botulinum Neurotoxin Complexes.Toxins · 2026Review
- Advances in Clostridial Neurotoxins: Passage of the Intestinal Barrier and Targeting of Specific Neuronal Cells.Toxins · 2026Review
- Single Particle Tracking Photo-Activated Localization Microscopy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Case Study: Illuminating the Nanoscale World of Microbiology.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Spatiotemporal Analysis of Super-resolved Live Cell Molecular Trajectory Data Using Nanoscale Spatiotemporal Indexing Clustering.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Nanoscale spatiotemporal cluster analysis of expressed and endogenous proteins.Nature protocols · 2025Review
- Nontoxic, multi-domain botulinum neurotoxin-LCHCVaccine · 2025Article
- Botulinum neurotoxin Light Chain/A1 uses fast synaptic vesicle cycling to cleave plasma membrane bound SNAP-25.Communications biology · 2025Article
- Review
- Botulinum neurotoxin A mutants with enhanced ganglioside binding show improved potency and altered ganglioside selectivity.Communications chemistry · 2025Article
- Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.Nature communications · 2025Article
- Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.Molecular imaging and biology · 2024Review
- Article
- Local Tetanus Begins with a Neuromuscular Junction Paralysis around the Site of Tetanus Neurotoxin Release due to Cleavage of the Vesicle-Associated Membrane Protein.The American journal of pathology · 2024Article
- Potency Evaluations of Recombinant Botulinum Neurotoxin A1 Mutants Designed to Reduce Toxicity.International journal of molecular sciences · 2024Article
- Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil.Neuroscience bulletin · 2024Review
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Authors and funding
21 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique nerve terminal targeting of botulinum neurotoxin type A (BoNT/A) is due to its capacity to bind two receptors on the neuronal plasma membrane: polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Whether and how PSGs and SV2 may coordinate other proteins for BoNT/A recruitment and internalization remains unknown. Here, we demonstrate that the targeted endocytosis of BoNT/A into synaptic vesicles (SVs) requires a tripartite surface nanocluster. Live-cell super-resolution imaging and electron microscopy of catalytically inactivated BoNT/A wildtype and receptor-binding-deficient mutants in cultured hippocampal neurons demonstrated that BoNT/A must bind coincidentally to a PSG and SV2 to target synaptic vesicles. We reveal that BoNT/A simultaneously interacts with a preassembled PSG-synaptotagmin-1 (Syt1) complex and SV2 on the neuronal plasma membrane, facilitating Syt1-SV2 nanoclustering that controls endocytic sorting of the toxin into synaptic vesicles. Syt1 CRISPRi knockdown suppressed BoNT/A- and BoNT/E-induced neurointoxication as quantified by SNAP-25 cleavage, suggesting that this tripartite nanocluster may be a unifying entry point for selected botulinum neurotoxins that hijack this for synaptic vesicle targeting.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.