{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:28:35Z","timestamp":1784914115504,"version":"3.55.0"},"reference-count":70,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MINECO, Ministerio de Econom\u00eda, Comercio y Empresa","award":["PID2021-126677NB-I00"],"award-info":[{"award-number":["PID2021-126677NB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Epsilon toxin (ETX) from Clostridium perfringens is a pore-forming toxin (PFT) that crosses the blood\u2013brain barrier and binds to myelin structures. In in vitro assays, ETX causes oligodendrocyte impairment, subsequently leading to demyelination. In fact, ETX has been associated with triggering multiple sclerosis. Myelin and lymphocyte protein (MAL) is widely considered to be the receptor for ETX as its presence is crucial for the effects of ETX on the plasma membrane of host cells that involve pore formation, resulting in cell death. To overcome the pores formed by PFTs, some host cells produce extracellular vesicles (EVs) to reduce the amount of pores inserted into the plasma membrane. The formation of EVs has not been studied for ETX in host cells. Here, we generated a highly sensitive clone from HeLa cells overexpressing the MAL-GFP protein in the plasma membrane. We observed that ETX induces the formation of EVs. Moreover, the MAL protein and ETX oligomers are found in these EVs, which are a very useful tool to decipher and study the mode of action of ETX and characterize the mechanisms involved in the binding of ETX to its receptor.<\/jats:p>","DOI":"10.3390\/toxins16120525","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T11:03:08Z","timestamp":1733310188000},"page":"525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Epsilon Toxin from Clostridium perfringens Induces the Generation of Extracellular Vesicles in HeLa Cells Overexpressing Myelin and Lymphocyte Protein"],"prefix":"10.3390","volume":"16","author":[{"given":"Jonatan","family":"Dorca-Ar\u00e9valo","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Laboratory of Molecular and Cellular Neurobiology, Bellvitge Biomedical Research Institute (IDIBELL), 08907 L\u2019Hospitalet de Llobregat, Spain"},{"name":"Institute of Neuroscience, Bellvitge Health Sciences Campus, University of Barcelona, Carrer de la Feixa Llarga, s\/n, 08907 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Santana-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2154-1167","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Torrej\u00f3n-Escribano","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Scientific and Technological Centers (CCiTUB), Bellvitge Campus, University of Barcelona, Carrer de la Feixa Llarga, s\/n, 08907 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-4664","authenticated-orcid":false,"given":"Mireia","family":"Mart\u00edn-Satu\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Oncobell Program, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), CIBERONC, 08908 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Blasi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences-Campus Bellvitge, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Laboratory of Molecular and Cellular Neurobiology, Bellvitge Biomedical Research Institute (IDIBELL), 08907 L\u2019Hospitalet de Llobregat, Spain"},{"name":"Institute of Neuroscience, Bellvitge Health Sciences Campus, University of Barcelona, Carrer de la Feixa Llarga, s\/n, 08907 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.3390\/toxins5112138","article-title":"Clostridium perfringens epsilon toxin: A malevolent molecule for animals and man?","volume":"5","author":"Stiles","year":"2013","journal-title":"Toxins"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0006-291X(77)90506-X","article-title":"Structural studies on epsilon-prototoxin of Clostridium perfringens type D. 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