{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:45:32Z","timestamp":1790178332960,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI118389"],"award-info":[{"award-number":["AI118389"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI030162"],"award-info":[{"award-number":["AI030162"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans but also are common therapies for neurological diseases. BoNTs are dichain toxins, comprising an N-terminal catalytic domain (LC) disulfide bond linked to a C-terminal heavy chain (HC) which includes a translocation domain (H\n            <jats:sub>N<\/jats:sub>\n            ) and a receptor binding domain (H\n            <jats:sub>C<\/jats:sub>\n            ). Recently, the BoNT serotype A (BoNT\/A) subtypes A1 and A2 were reported to possess similar potencies but different rates of cellular intoxication and pathology in a mouse model of botulism. The current study measured H\n            <jats:sub>C<\/jats:sub>\n            A1 and H\n            <jats:sub>C<\/jats:sub>\n            A2 entry into rat primary neurons and cultured Neuro2A cells. We found that there were two sequential steps during the association of BoNT\/A with neurons. The initial step was ganglioside dependent, while the subsequent step involved association with synaptic vesicles. H\n            <jats:sub>C<\/jats:sub>\n            A1 and H\n            <jats:sub>C<\/jats:sub>\n            A2 entered the same population of synaptic vesicles and entered cells at similar rates. The primary difference was that H\n            <jats:sub>C<\/jats:sub>\n            A2 had a higher degree of receptor occupancy for cells and neurons than HcA1. Thus, H\n            <jats:sub>C<\/jats:sub>\n            A2 and H\n            <jats:sub>C<\/jats:sub>\n            A1 share receptors and entry pathway but differ in their affinity for receptor. The initial interaction of H\n            <jats:sub>C<\/jats:sub>\n            A1 and H\n            <jats:sub>C<\/jats:sub>\n            A2 with neurons may contribute to the unique pathologies of BoNT\/A1 and BoNT\/A2 in mouse models.\n          <\/jats:p>","DOI":"10.1128\/iai.00795-16","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T20:14:05Z","timestamp":1476821645000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Entry of Botulinum Neurotoxin Subtypes A1 and A2 into Neurons"],"prefix":"10.1128","volume":"85","author":[{"given":"Abby R.","family":"Kroken","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith C.","family":"Blum","sequence":"additional","affiliation":[{"name":"Department of 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