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Synaptotagmin 1 mediates toxicity of botulinum neurotoxin type A
Open accessPreprint — published as 10.15252/embj.2022112095 · Paper page
Abstract
The extreme neurotoxicity of botulinum neurotoxins (BoNTs), broadly used as a therapeutics, is mediated by their direct binding to two plasma membrane receptors: polysialogangliosides (PSGs) and serotype-dependently either synaptotagmin 1/2 (Syt1/2) or synaptic vesicle glycoprotein 2 (SV2). Here, we demonstrate that although BoNT/A serotype binds directly to PSG and SV2, its neurotoxicity depends on Syt1. Using single-molecule superresolution microscopy of pathological concentrations of BoNT/A holotoxins, we demonstrate that the toxin binds to a preassembled PSG-Syt1 complex that forms nanoclusters with SV2 on the plasma membrane of hippocampal neurons. This coincidental interaction controls the selective endocytic targeting of BoNT/A into synaptic vesicles, leading to incapacitation of neuronal communication. Our results suggest that Syt1-SV2 plasma membrane nanoclusters may acts as a common target for various BoNT serotypes. One-Sentence Summary: BoNT/A hijacks an intrinsic tripartite PSG-Syt1-SV2 endocytic sorting mechanism to incapacitate neuronal communication
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Research works printed but not linked: 34
- 10.1128/MMBR.46.1.86-94.1982 · DOI
- 10.1124/pr.116.012658 · DOI
- 10.1146/annurev-biochem-013118-111654 · DOI
- 10.1016/0968-0004(86)90282-3 · DOI
- 10.1007/82_2016_48 · DOI
- 10.1101/2021.12.08.471864 · DOI
- 10.1523/JNEUROSCI.4781-09.2010 · DOI · Paper page
- 10.1074/jbc.M407502200 · DOI
- 10.1126/science.1214270 · DOI
- 10.1371/journal.pone.0019764 · DOI
- 10.1038/nsb879 · DOI
- 10.1126/science.1088525 · DOI
- 10.1126/science.1152089 · DOI · Paper page
- 10.1242/jcs.146340 · DOI
- 10.1007/978-1-62703-137-0_7 · DOI
- 10.1523/JNEUROSCI.4248-14.2015 · DOI · Paper page
- 10.1101/2021.09.08.459552 · DOI
- 10.1016/j.febslet.2014.02.034 · DOI
- 10.1038/nsmb.3245 · DOI
- 10.1074/jbc.M000674200 · DOI
- 10.1523/JNEUROSCI.0210-20.2020 · DOI
- 10.1074/jbc.M403945200 · DOI
- 10.1073/pnas.1908051116 · DOI
- 10.1007/978-3-642-33570-9_4 · DOI
- 10.1046/j.1365-2958.2003.03872.x · DOI
- 10.1038/nprot.2017.116 · DOI
- 10.1083/jcb.201604001 · DOI
- 10.1038/s41586-021-03828-1 · DOI · Paper page
- 10.3389/fncel.2017.00234 · DOI · Paper page
- 10.1016/j.bbamcr.2014.11.014 · DOI
- 10.1038/s41598-020-62202-9 · DOI
- 10.1371/journal.ppat.1008656 · DOI
- 10.1073/pnas.2001119117 · DOI
- 10.1073/pnas.2024893118 · DOI
Metadata
- Authors
- Joensuu, M., Lanoue, V., Syed, P., Wallis, T. P., Rae, J., Blum, A., Gormal, R., Small, C., Sanders, S., Jiang, A., Mahrhold, S., Krez, N., Cousin, M., Cooper-White, R., Cooper-White, J. J., Collins, B. M., Parton, R. G., Balistreri, G., Rummel, A., & Meunier, F. A.
- Affiliations
- The University of Queensland (AU)
- Medizinische Hochschule Hannover (DE)
- Simons Initiative for the Developing Brain (GB)
- University of Helsinki (FI)
- Corresponding author
- Joensuu, Merja
- Meunier, Frédéric A.
- ORCID
- Venue
- The EMBO Journal
- Publisher
- openRxiv
- Published
- 2022-03-01
- Volume
- 42
- Issue
- 13
- Pages
- e112095-e112095
- ISSN
- 0261-4189 (ISSN-L)
- PMC
- PMC10308369
- OpenAlex
- W4378172982
- Cited by
- 34
- References
- 1
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 9 · 2023: 4
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Helsingin Yliopisto
- University of Queensland
- Academy of Finland (318434)
- Bundesministerium für Bildung und Forschung (031L0111B)
- Department of Health and Aged Care, Australian Government (1140064, 1156489, 1120381, 1155794, 1136021, 1150083)
- Department of Education and Training (LE130100078, DE190100565)
- Allergan
- Helsinki Institute of Life Science, Helsingin Yliopisto
- Medical Research Council
- National Health and Medical Research Council (1140064, 1120381, 1150083, 1155794, 1156489, 1136021)
- Queensland Brain Institute (LE130100078)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Botulinum Toxin and Related Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- botulinum toxin type A, botulinum neurotoxin type E, polysialogangliosides, SV2, synaptotagmin-1, synaptic vesicle endocytosis, toxin internalization, SNAP-25 cleavage, hippocampal neurons, receptor binding
- MeSH terms
- Animals, Cell Membrane, Gangliosides, Membrane Glycoproteins, Nerve Tissue Proteins, Synaptic Vesicles, Botulinum Toxins, Type A, Rats
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