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Tcn\u03b1 binds to sulfated glycosaminoglycans (sGAG) for cell-surface attachment and utilizes low-density lipoprotein receptor (LDLR) for rapid entry. However, it was also shown that Tcn\u03b1 may use alternative entry receptors other than LDLR. Here, we define that LRP1 and Megalin can also facilitate the cellular entry of Tcn\u03b1 by employing reconstitutive LDLR family proteins. LDLR, LRP1, and Megalin recognize Tcn\u03b1 via their ligand-binding domains (also known as LDL receptor type A repeats). Notably, LDLR and LRP1 have contrasting expression levels in many different cells, thus the dominant entry receptor for Tcn\u03b1 could be cell-type dependent. These findings together increase our knowledge of the Tcn\u03b1 actions and further help to understand the pathogenesis of <jats:italic>C. novyi<\/jats:italic> infection-associated diseases.<\/jats:p>","DOI":"10.1038\/s42003-022-03873-0","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T08:14:47Z","timestamp":1662452087000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["LDLR, LRP1, and Megalin redundantly participate in the uptake of Clostridium novyi alpha-toxin"],"prefix":"10.1038","volume":"5","author":[{"given":"Yao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-6642","authenticated-orcid":false,"given":"Danyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diyin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-3213","authenticated-orcid":false,"given":"Liuqing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-115X","authenticated-orcid":false,"given":"Jianhua","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-698X","authenticated-orcid":false,"given":"Liang","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"3873_CR1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1128\/CMR.3.1.66","volume":"3","author":"CL Hatheway","year":"1990","unstructured":"Hatheway, C. 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