Document Type
Article
Publication Date
9-2025
Publisher
Nature Publishing
Source Publication
Communications Biology
Source ISSN
2399-3642
Abstract
Botulinum neurotoxins (BoNT) are the most potent protein toxins for humans, yet how BoNT-Light Chain/A1 (LC/A1) journeys to cleave intracellular SNAP-25 is understudied. Here we use a cell-based assay to measure cytosolic EGFP-LC/A1 intracellular trafficking and SNAP-25 cleavage in Neuro-2A cells. Intracellular LC/A1 associated on microtubules and co-localized with Rab GTPases involved in fast synaptic vesicles and endosome recycling. Multiple Dominant Negative (DN) Rabs GTPases involved in fast synaptic vesicles or endosome recycling inhibited LC/A1 trafficking to the intracellular plasma membrane and SNAP-25 cleavage. A cytosolic LC/A1 variant that bound the plasma membrane from the cytosol was insensitive to DNRab GTPases involved in fast synaptic vesicle recycling. LC/A1 traffics on fast synaptic vesicles to the intracellular plasma membrane to cleave SNAP-25. Our data suggest, like Heavy Chain host cell entry and LC catalysis, LC intracellular trafficking to target host substrates can contribute to bacterial toxin potency.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Gardner, Alexander; Sneller, Molly; Tepp, William H.; Barbieri, Joseph T.; and Pellett, Sabine, "Botulinum Neurotoxin Light Chain/A1 Uses Fast Synaptic Vesicle Cycling to Cleave Plasma Membrane Bound SNAP-25" (2025). College of Nursing Faculty Research and Publications. 1222.
https://epublications.marquette.edu/nursing_fac/1222
Comments
Published version. Communications Biology, Vol. 8 (2025). DOI. This article is © 2025 The Authors.
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/bync-nd/4.0/.
Alexander Gardner was affiliated with Medical College of Wisconsin, Milwaukee, at the time of publication.