Shiga toxin 1 interaction with enterocytes causes apical protein mistargeting through the depletion of intracellular galectin-3

Marina Laiko, Rakhilya Murtazina, Irina Malyukova, Chengru Zhu, Edgar C. Boedeker, Oksana Gutsal, Robert O'Malley, Robert N. Cole, Phillip I. Tarr, Karen F. Murray, Anne Kane, Mark Donowitz, Olga Kovbasnjuk

Research output: Contribution to journalArticle

Abstract

Shiga toxins (Stx) 1 and 2 are responsible for intestinal and systemic sequelae of infection by enterohemorrhagic Escherichia coli (EHEC). However, the mechanisms through which enterocytes are damaged remain unclear. While secondary damage from ischemia and inflammation are postulated mechanisms for all intestinal effects, little evidence excludes roles for more primary toxin effects on intestinal epithelial cells. We now document direct pathologic effects of Stx on intestinal epithelial cells. We study a well-characterized rabbit model of EHEC infection, intestinal tissue and stool samples from EHEC-infected patients, and T84 intestinal epithelial cells treated with Stx1. Toxin uptake by intestinal epithelial cells in vitro and in vivo causes galectin-3 depletion from enterocytes by increasing the apical galectin-3 secretion. This Shiga toxin-mediated galectin-3 depletion impairs trafficking of several brush border structural proteins and transporters, including villin, dipeptidyl peptidase IV, and the sodium-proton exchanger 2, a major colonic sodium absorptive protein. The mistargeting of proteins responsible for the absorptive function might be a key event in Stx1-induced diarrhea. These observations provide new evidence that human enterocytes are directly damaged by Stx1. Conceivably, depletion of galectin-3 from enterocytes and subsequent apical protein mistargeting might even provide a means whereby other pathogens might alter intestinal epithelial absorption and produce diarrhea.

Original languageEnglish (US)
Pages (from-to)657-666
Number of pages10
JournalExperimental cell research
Volume316
Issue number4
DOIs
StatePublished - Feb 15 2010

Keywords

  • NHE2
  • Shiga toxin
  • apical protein missorting
  • enterocytes
  • galectin-3 secretion

ASJC Scopus subject areas

  • Cell Biology

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