Shiga Toxin Is Transported into the Nucleoli of Intestinal Epithelial Cells via a Carrier-Dependent Process 英文参考文献.docVIP

Toxins 2010, 2, 1318-1335; doi:10.3390/toxins2061318 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Article Shiga Toxin Is Transported into the Nucleoli of Intestinal Epithelial Cells via a Carrier-Dependent Process Boris Baibakov, Rakhilya Murtazina, Christian Elowsky, Francis M. Giardiello and Olga Kovbasnjuk * GI Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; E-Mails: BorisB@ (B.B.); rakhilya@ (R.M.); celowsky21@ (C.E.); fgiardi@ (F.M.G.) * Author to whom correspondence should be addressed; E-Mail: okovbas1@; Tel.: +410-614-0128; Fax: +410-955-9677. Received: 22 April 2010; in revised form: 19 May 2010 / Accepted: 3 June 2010 / Published: 7 June 2010 Abstract: Shiga toxin (Stx) produced by the invasive Shigella dysenteriae serotype 1 (S. dysenteriae1) causes gastrointestinal and kidney complications. It has been assumed that Stx is released intracellularly after enterocyte invasion by S. dysenteriae1. However, there is little information about Stx distribution inside S. dysenteriae1-infected enterocytes. Here, we use intestinal epithelial T84 cells to characterize the trafficking of Stx delivered into the cytosol, in ways that mimic aspects of S. dysenteriae1 infection. We find that cytoplasmic Stx is transported into nucleoli. Stx nucleolar movement is carrier- and energy-dependent. Stx binding to the nucleoli of normal human enterocytes in vitro supports possible roles for nucleolar trafficking in toxin-induced intestinal pathology. Keywords: Shiga toxin; nucleolar trafficking; intestinal epithelial cells 1. Introduction The illnesses caused by the Shiga toxin (Stx)-producing bacteria Shigella dysenteriae serotype 1 (S. dysenteriae1) can produce fever, fatigue, anorexia, watery and bloody diarrhea, and often progresses to dysentery and the hemolytic uremic syndrome [1–3]. Stx-related pathology has been intensive