title: Latrunculin B facilitates Shiga toxin 1 transcellular transcytosis across T84 intestinal epithelial cells.
abstract: Shiga toxins (Stx), released into the intestinal lumen by enterohemorrhagic Escherichia coli (EHEC), are major virulence factors responsible for gastrointestinal and systemic illnesses. These pathologies are believed to be due to the action of the toxins on endothelial cells, which express the Stx receptor, the glycosphingolipid Gb3. To reach the endothelial cells, Stx must translocate across the intestinal epithelial monolayer. This process is poorly understood. We investigated Stx1 movement across the intestinal epithelial T84 cell model and the role of actin turnover in this transcytosis. We showed that changes in the actin cytoskeleton due to latrunculin B, but not cytochalasin D or jasplakinolide, significantly facilitate toxin transcytosis across T84 monolayers. This trafficking is transcellular and completely inhibited by tannic acid, a cell impermeable plasma membrane fixative. This indicates that actin turnover could play an important role in Stx1 transcellular transcytosis across intestinal epithelium in vitro. Since EHEC attachment to epithelial cells causes an actin rearrangement, this finding may be highly relevant to Stx-induced disease.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Maluykova
authors.forename: Oksana
authors.initials: O
authors.lastname: Gutsal
authors.forename: Marina
authors.initials: M
authors.lastname: Laiko
authors.forename: Anne
authors.initials: A
authors.lastname: Kane
authors.forename: Mark
authors.initials: M
authors.lastname: Donowitz
authors.forename: Olga
authors.initials: O
authors.lastname: Kovbasnjuk
mesh_terms: D000199:Actins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D047630:Depsipeptides / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D022622:Shiga Toxin 1 / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D047630:Depsipeptides; D003911:Dextrans; D022622:Shiga Toxin 1; D053778:Thiazolidines; C057531:jasplakinolide; D015638:Cytochalasin D; C037068:latrunculin B