Dissertation/Thesis Abstract

Enteropathogenic E. coli EspG1/G2 Perturb Microtubules and Impede Tight Junction Regulation and Recovery
by Glotfelty, Lila Gollogly, Ph.D., University of Illinois at Chicago, 2014, 126; 3639583
Abstract (Summary)

The intestinal epithelial tight junction (TJ) is a dynamic structure, with multiple proteins constitutively recycling between the membrane and the cytosol. The mechanisms required for maintaining the TJ in the homeostatic state and for TJ restoration are not well described. Herein we show for the first time that occludin traffics on microtubules. We also demonstrate that these structures are required for maintaining TJ structure and function. Using the calcium switch assay, we establish that microtubules and dynein-mediated trafficking are required for complete TJ restoration after insult. Interruption of homeostatic TJ protein recycling presents as an intuitive way to disrupt barrier function. Enteropathogenic E. coli (EPEC) is an enteric pathogen that induces loss of TJ structure and function. TJ restoration has not been studied with respect to EPEC pathogenesis. Our data establish for the first time that EPEC effector proteins stimulate internalization of occludin and impede TJ restoration. Effector proteins EspG1/G2 disrupt microtubules (MTs). We show that intact MTs promote barrier recovery after EPEC infection. We also demonstrate that EspG1/G2-mediated MT disruption leads to TJ dysregulation and inhibition of TJ restoration. EspG was recently shown to interact with ARF and PAK small GTPases. This report shows that EspG’s impact on MTs is independent of its modulation of GTPase signaling, suggesting a broader scope of action for EspG. Taken together, these data illuminate a new MT-dependent aspect of TJ regulation, and suggest that EPEC sabotages host cell protein recycling, preventing TJ restoration and perpetuating loss of barrier function.

Indexing (document details)
Advisor: Freitag, Nancy
Commitee: Hecht, Gail
School: University of Illinois at Chicago
Department: Microbiology and Immunology
School Location: United States -- Illinois
Source: DAI-B 76/01(E), Dissertation Abstracts International
Subjects: Cellular biology, Microbiology
Keywords: Dynein, Enteropathogenic E. coli, Kinesin, Microtubules, Occludin, Recycling, Tight junctions
Publication Number: 3639583
ISBN: 978-1-321-24140-2
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