Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics

Heidi Hehnly; David Sheff; Mark Stamnes

doi:10.1091/mbc.E06-04-0310

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Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics

Journal article

Open access

Peer reviewed

Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics

Heidi Hehnly, David Sheff and Mark Stamnes

Molecular biology of the cell, Vol.17(10), pp.4379-4389

10/2006

DOI: 10.1091/mbc.E06-04-0310

PMCID: PMC1635369

PMID: 16885418

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Abstract

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 after 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 retrograde transport of the toxin through the secretory pathway.

Animals

Cercopithecus aethiops

Dyneins - physiology

Endosomes - drug effects

Endosomes - metabolism

Fluorescent Antibody Technique

Golgi Apparatus - drug effects

Golgi Apparatus - metabolism

Microtubules - drug effects

Microtubules - metabolism

Microtubules - ultrastructure

Protein Transport

Shiga Toxin - pharmacology

Time Factors

Transferrin - metabolism

Vero Cells

Details

Title: Subtitle: Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics
Creators: Heidi Hehnly - Roy J. and Lucille A. Carver College of Medicine
David Sheff - Roy J. and Lucille A. Carver College of Medicine
Mark Stamnes - Departments of *Physiology and Biophysics and
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.17(10), pp.4379-4389
DOI: 10.1091/mbc.E06-04-0310
PMID: 16885418
PMCID: PMC1635369
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: GM-068674 / NIGMS NIH HHS R01 GM068674 / NIGMS NIH HHS
Language: English
Date published: 10/2006
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984297598502771

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