Document Type
Article
Publication Date
10-2021
Publisher
MDPi
Source Publication
International Journal of Molecular Sciences
Source ISSN
1661-6596
Original Item ID
DOI: 10.3390/ijms222011115
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.