Document Type
Article
Publication Date
10-2021
Publisher
MDPi
Source Publication
International Journal of Molecular Sciences
Source ISSN
1661-6596
Abstract
Botulinum neurotoxin serotype A (BoNT/A) is the most potent protein toxin to humans. BoNT/A light chain (LC/A) cleavage of the membrane-bound SNAP-25 has been well-characterized, but how LC/A traffics to the plasma membrane to target SNAP-25 is unknown. Of the eight BoNT/A subtypes (A1–A8), LC/A3 has a unique short duration of action and low potency that correlate to the intracellular steady state of LC/A, where LC/A1 is associated with the plasma membrane and LC/A3 is present in the cytosol. Steady-state and live imaging of LC/A3-A1 chimeras identified a two-step process where the LC/A N terminus bound intracellular vesicles, which facilitated an internal α-helical-rich domain to mediate LC/A plasma membrane association. The propensity of LC/A variants for membrane association correlated with enhanced BoNT/A potency. Understanding the basis for light chain intracellular localization provides insight to mechanisms underlying BoNT/A potency, which can be extended to applications as a human therapy.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Gardner, Alexander; Tepp, William H.; Bradshaw, Marite; Barbieri, Joseph T.; and Pellett, Sabine, "Resolution of Two Steps in Botulinum Neurotoxin Serotype A1 Light Chain Localization to the Intracellular Plasma Membrane" (2021). College of Nursing Faculty Research and Publications. 1183.
https://epublications.marquette.edu/nursing_fac/1183
Comments
Published version. International Journal of Molecular Sciences, Vol. 22, No. 20 (2021). DOI. © 2021 The Authors, published by MDPI. Used with permission.
Alexander Gardner was affiliated with Medical College of Wisconsin, Milwaukee, at the time of publication.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).