ArticleThe Journal of biological chemistry2011
Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 157 citations in OpenAlex.
- Role of the Host Membrane Trafficking Protein Dynamin 2 in Cell-to-Cell Spread of Bacterial Pathogens.Cells · 2026Review
- Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.Biogerontology · 2026Review
- Electrical or magnetic nerve stimulation enhance the BoNT/A-mediated muscle paralysis.Journal of neuroengineering and rehabilitation · 2026Article
- Humanized VHH-hFc Fusion Proteins Targeting the L-HN Fragment of Tetanus Toxin Provided Protection In Vivo.Antibodies (Basel, Switzerland) · 2025Article
- Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Botulinum Neurotoxins as Two-Faced Janus Proteins.Biomedicines · 2025Review
- 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
- The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model.Stem cell research & therapy · 2024Article
- Article
- Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR.bioRxiv : the preprint server for biology · 2024Article
- Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters.Nature communications · 2024Article
- Mechanisms of aquaporin-4 vesicular trafficking in mammalian cells.Journal of neurochemistry · 2024Article
- Tetanus toxin and botulinum neurotoxin-derived fusion molecules are effective bivalent vaccines.Applied microbiology and biotechnology · 2023Article
- The sulfonadyns: a class of aryl sulfonamides inhibiting dynamin I GTPase and clathrin mediated endocytosis are anti-seizure in animal models.RSC medicinal chemistry · 2023Article
- Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG-Syt1-SV2 plasma membrane nanocluster for synaptic vesicle entry.The EMBO journal · 2023Article
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
- Prodrugs of the Archetypal Dynamin Inhibitor Bis-T-22.ChemMedChem · 2022Article
- Cellular and structural insight into dynamin function during endocytic vesicle formation: a tale of 50 years of investigation.Bioscience reports · 2022Review
- Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to the plasma membrane of cholinergic motor nerve terminals, BoNTs are internalized into an endocytic compartment. Although several endocytic pathways have been characterized in neurons, the molecular mechanism underpinning the uptake of BoNTs at the presynaptic nerve terminal is still unclear. Here, a recombinant BoNT/A heavy chain binding domain (Hc) was used to unravel the internalization pathway by fluorescence and electron microscopy. BoNT/A-Hc initially enters cultured hippocampal neurons in an activity-dependent manner into synaptic vesicles and clathrin-coated vesicles before also entering endosomal structures and multivesicular bodies. We found that inhibiting dynamin with the novel potent Dynasore analog, Dyngo-4a(TM), was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms.
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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.