Clathrin-dependent trafficking of subtilase cytotoxin, a novel AB(5) toxin that targets the endoplasmic reticulum chaperone BiP
Date
2008
Authors
Chong, D.
Paton, J.
Thorpe, C.
Paton, A.
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Advisors
Journal Title
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Type:
Journal article
Citation
Cellular Microbiology, 2008; 10(3):795-806
Statement of Responsibility
Damien C. Chong, James C. Paton, Cheleste M. Thorpe and Adrienne W. Paton
Conference Name
Abstract
Subtilase cytotoxin (SubAB) is the prototype of a new family of AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. Its cytotoxic activity is due to its capacity to enter cells and specifically cleave the endoplasmic reticulum (ER) chaperone BiP. However, its trafficking within target cells has not been investigated previously. In Vero cells, fluorescence colocalization with subcellular markers established that SubAB is trafficked from the cell surface to the ER via a retrograde pathway similar, but not identical, to those of Shiga toxin (Stx) and cholera toxin (Ctx), with their pathways converging at the Golgi. The clathrin inhibitor phenylarsine oxide prevented SubAB entry and BiP cleavage in SubAB-treated Vero, HeLa and N2A cells, while cholesterol depletion did not, demonstrating that, unlike either Stx or Ctx, SubAB internalization is exclusively clathrin-dependent.
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Dissertation Note
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© 2008 Blackwell Publishing Ltd