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MBC in Press, published online ahead of print August 2, 2006
Mol. Biol. Cell 10.1091/mbc.E06-04-0310

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Submitted on April 17, 2006
Revised on July 3, 2006
Accepted on July 21, 2006

Shiga Toxin Facilitates Its Retrograde Transport by Modifying Microtubule Dynamics

Heidi Hehnly,* David Sheff,{dagger} and Mark Stamnes*

Departments of *Physiology and Biophysics and {dagger}Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242

Monitoring Editor: Adam Linstedt

The bacterial exotoxin, Shiga toxin, is endocytosed by mammalian host cells and transported retrogradely through the secretory pathway before entering the cytosol. Shiga toxin also increases the levels of microfilaments and microtubules (MTs) upon binding to the cell surface. The purpose for this alteration in cytoskeletal dynamics is unknown. We have investigated whether Shiga-toxin-induced changes in MT levels facilitate its intracellular transport. We have tested the effects of the Shiga toxin B subunit (STB) on MT-dependent and independent transport steps. STB increases the rate of MT-dependent Golgi stack repositioning following nocodazole treatment. It also enhances the MT-dependent accumulation of transferrin in a perinuclear recycling compartment. By contrast, the rate of MT-independent transferrin recycling is not significantly different when STB is present. We found that STB normally requires MTs and dynein for its retrograde transport to the juxtanuclear Golgi complex and that STB increases MT assembly. Furthermore, we find that MT polymerization is limiting for STB transport in cells. These results show that STB-induced changes in cytoskeletal dynamics influence intracellular transport. We conclude that the increased rate of MT assembly upon Shiga toxin binding facilitates the toxin’s retrograde transport through the secretory pathway.


Address correspondence to: Mark Stamnes (mark-stamnes{at}uiowa.edu)




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M. L. Torgersen, S. Walchli, S. Grimmer, S. S. Skanland, and K. Sandvig
Protein Kinase C{delta} Is Activated by Shiga Toxin and Regulates Its Transport
J. Biol. Chem., June 1, 2007; 282(22): 16317 - 16328.
[Abstract] [Full Text] [PDF]




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