{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:17:08Z","timestamp":1792675028449,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI139306"],"award-info":[{"award-number":["AI139306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013A8), 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 \u03b1-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.<\/jats:p>","DOI":"10.3390\/ijms222011115","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T13:35:47Z","timestamp":1634304947000},"page":"11115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Resolution of Two Steps in Botulinum Neurotoxin Serotype A1 Light Chain Localization to the Intracellular Plasma Membrane"],"prefix":"10.3390","volume":"22","author":[{"given":"Alexander","family":"Gardner","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 Watertown Plank Rd,  Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Tepp","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marite","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin, 8701 Watertown Plank Rd,  Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Pellett","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Dr, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins Affecting Neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. 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