Journal article
Retrograde Shiga Toxin Trafficking Is Regulated by ARHGAP21 and Cdc42
Molecular biology of the cell, Vol.20(20), pp.4303-4312
10/15/2009
DOI: 10.1091/mbc.E09-02-0155
PMCID: PMC2762141
PMID: 19692570
Abstract
Shiga-toxin-producing Escherichia coli remain a food-borne health threat. Shiga toxin is endocytosed by intestinal epithelial cells and transported retrogradely through the secretory pathway. It is ultimately translocated to the cytosol where it inhibits protein translation. We found that Shiga toxin transport through the secretory pathway was dependent on the cytoskeleton. Recent studies reveal that Shiga toxin activates signaling pathways that affect microtubule reassembly and dynein-dependent motility. We propose that Shiga toxin alters cytoskeletal dynamics in a way that facilitates its transport through the secretory pathway. We have now found that Rho GTPases regulate the endocytosis and retrograde motility of Shiga toxin. The expression of RhoA mutants inhibited endocytosis of Shiga toxin. Constitutively active Cdc42 or knockdown of the Cdc42-specific GAP, ARHGAP21, inhibited the transport of Shiga toxin to the juxtanuclear Golgi apparatus. The ability of Shiga toxin to stimulate microtubule-based transferrin transport also required Cdc42 and ARHGAP21 function. Shiga toxin addition greatly decreases the levels of active Cdc42-GTP in an ARHGAP21-dependent manner. We conclude that ARHGAP21 and Cdc42-based signaling regulates the dynein-dependent retrograde transport of Shiga toxin to the Golgi apparatus.
Details
- Title: Subtitle
- Retrograde Shiga Toxin Trafficking Is Regulated by ARHGAP21 and Cdc42
- Creators
- Heidi Hehnly - Roy J. and Lucille A. Carver College of MedicineKatrina Marie Longhini - Institute of Molecular Biology and BiophysicsJi-Long Chen - Roy J. and Lucille A. Carver College of MedicineMark Stamnes - Institute of Molecular Biology and Biophysics
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.20(20), pp.4303-4312
- Publisher
- Amer Soc Cell Biology
- DOI
- 10.1091/mbc.E09-02-0155
- PMID
- 19692570
- PMCID
- PMC2762141
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Number of pages
- 10
- Grant note
- 0715567Z; 0950167G / American Heart Association R01GM068674 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM-068674 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Dr. Ramon D. Buckley student scholarship fund, Department of Molecular Physiology and Biophysics, University of Iowa
- Language
- English
- Date published
- 10/15/2009
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297511602771
Metrics
28 Record Views