QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online May 4, 2004
doi: 10.1242/10.1242/jcs.01081

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lauvrak, S. U. Articles by Sandvig, K. Search for Related Content PubMed PubMed Citation Articles by Lauvrak, S. U. Articles by Sandvig, K.

Efficient endosome-to-Golgi transport of Shiga toxin is dependent on dynamin and clathrin

Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway

^* Author for correspondence (e-mail: ksandvig{at}radium.uio.no)

Accepted 5 January 2004

It has previously been shown that Shiga toxin, despite being bound to a glycolipid receptor, can be efficiently endocytosed from clathrin-coated pits. However, clathrin-independent endocytosis is also responsible for a proportion of the toxin uptake in some cells. After endocytosis the toxin can be transported in retrograde fashion to the Golgi apparatus and the endoplasmic reticulum, and then to the cytosol, where it exerts its toxic effect by inactivating ribosomes. In order to investigate the role of dynamin and clathrin in endosome-to-Golgi transport of Shiga toxin, we have used HeLa dyn^K44A and BHK antisense clathrin heavy chain (CHC) cells that, in an inducible manner, express mutant dynamin or CHC antisense RNA, respectively. In these cell lines, one can study the role of dynamin and clathrin on endosome-to-Golgi transport because they, as shown here, still internalize Shiga toxin when dynamin- and clathrin-dependent endocytosis is blocked. Butyric acid has been shown to sensitize A431 cells to Shiga toxin by increasing the proportion of cell-associated toxin that is transported to the Golgi apparatus and the endoplasmic reticulum. Here, we find that, in HeLa and BHK cells also, butyric acid also increased toxin transport to the Golgi apparatus and sensitized the cells to Shiga toxin. We have therefore studied the role of dynamin and clathrin in both untreated and butyric-acid-treated cells by measuring the sulfation of a modified Shiga B fragment. Our results indicate that endosome-to-Golgi transport of Shiga toxin is dependent on functional dynamin in both untreated cells and in cells treated with butyric acid. Interestingly, the regulation of Shiga toxin transport in untreated and butyric-acid-treated cells differs when it comes to the role of clathrin, because only cells that are sensitized to Shiga toxin with butyric acid need functional clathrin for endosome-to-Golgi transport.

Key words: Shiga toxin, Clathrin, Dynamin, Golgi apparatus

Related articles in JCS:

Shiga toxin: transporting an unwelcome visitor

JCS 2004 117: 1103. [Full Text]  

This article has been cited by other articles:

				J. B. Saenz, T. A. Doggett, and D. B. Haslam Identification and Characterization of Small Molecules That Inhibit Intracellular Toxin Transport Infect. Immun., September 1, 2007; 75(9): 4552 - 4561. [Abstract] [Full Text] [PDF]

				P. J. Tam and C. A. Lingwood Membrane cytosolic translocation of verotoxin A1 subunit in target cells Microbiology, August 1, 2007; 153(8): 2700 - 2710. [Abstract] [Full Text] [PDF]

				E. Fuchs, A. K. Haas, R. A. Spooner, S.-i. Yoshimura, J. M. Lord, and F. A. Barr Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways J. Cell Biol., July 30, 2007; 177(6): 1133 - 1143. [Abstract] [Full Text] [PDF]

				M. V. Bujny, V. Popoff, L. Johannes, and P. J. Cullen The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network J. Cell Sci., June 15, 2007; 120(12): 2010 - 2021. [Abstract] [Full Text] [PDF]

				V. Popoff, G. A. Mardones, D. Tenza, R. Rojas, C. Lamaze, J. S. Bonifacino, G. Raposo, and L. Johannes The retromer complex and clathrin define an early endosomal retrograde exit site J. Cell Sci., June 15, 2007; 120(12): 2022 - 2031. [Abstract] [Full Text] [PDF]

				M. Amessou, A. Fradagrada, T. Falguieres, J. M. Lord, D. C. Smith, L. M. Roberts, C. Lamaze, and L. Johannes Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins J. Cell Sci., April 15, 2007; 120(8): 1457 - 1468. [Abstract] [Full Text] [PDF]

				V. Rybakin, N. V. Gounko, K. Spate, S. Honing, I. V. Majoul, R. Duden, and A. A. Noegel Crn7 Interacts with AP-1 and Is Required for the Maintenance of Golgi Morphology and Protein Export from the Golgi J. Biol. Chem., October 13, 2006; 281(41): 31070 - 31078. [Abstract] [Full Text] [PDF]

				H. Hehnly, D. Sheff, and M. Stamnes Shiga Toxin Facilitates Its Retrograde Transport by Modifying Microtubule Dynamics Mol. Biol. Cell, October 1, 2006; 17(10): 4379 - 4389. [Abstract] [Full Text] [PDF]

				S. U. Lauvrak, S. Walchli, T.-G. Iversen, H. H. Slagsvold, M. L. Torgersen, B. Spilsberg, and K. Sandvig Shiga Toxin Regulates Its Entry in a Syk-dependent Manner Mol. Biol. Cell, March 1, 2006; 17(3): 1096 - 1109. [Abstract] [Full Text] [PDF]