{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:18:44Z","timestamp":1791321524576,"version":"4.3.1"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,9,29]]},"abstract":"<jats:p>Botulinum neurotoxins (BoNTs) cause botulism by entering neurons and cleaving proteins that mediate neurotransmitter release; disruption of exocytosis results in paralysis and death. The receptors for BoNTs are thought to be composed of both proteins and gangliosides; however, protein components that mediate toxin entry have not been identified. Using gain-of-function and loss-of-function approaches, we report here that the secretory vesicle proteins, synaptotagmins (syts) I and II, mediate the entry of BoNT\/B (but not BoNT\/A or E) into PC12 cells. Further, we demonstrate that BoNT\/B entry into PC12 cells and rat diaphragm motor nerve terminals was activity dependent and can be blocked using fragments of syt II that contain the BoNT\/B-binding domain. Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT\/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT\/B.<\/jats:p>","DOI":"10.1083\/jcb.200305098","type":"journal-article","created":{"date-parts":[[2003,9,22]],"date-time":"2003-09-22T21:36:04Z","timestamp":1064266564000},"page":"1293-1303","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":270,"title":["Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells"],"prefix":"10.1083","volume":"162","author":[{"given":"Min","family":"Dong","sequence":"first","affiliation":[{"name":"1Department of Physiology and the Neuroscience Training Program, University of Wisconsin, Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Richards","sequence":"additional","affiliation":[{"name":"1Department of Physiology and the Neuroscience Training Program, University of Wisconsin, Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Goodnough","sequence":"additional","affiliation":[{"name":"2Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, Madison, WI 53706"},{"name":"3Metabiologics, Inc., Madison, WI 53719"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Tepp","sequence":"additional","affiliation":[{"name":"2Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"2Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin R.","family":"Chapman","sequence":"additional","affiliation":[{"name":"1Department of Physiology and the Neuroscience Training Program, University of Wisconsin, Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,9,22]]},"reference":[{"key":"2023072214364239000_BIB1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","volume":"285","year":"2001","journal-title":"JAMA."},{"key":"2023072214364239000_BIB2","doi-asserted-by":"crossref","first-page":"25427","DOI":"10.1074\/jbc.M906729199","volume":"275","year":"2000","journal-title":"J. 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