Spooner, Robert A., Watson, Peter, Smith, Daniel C., Boal, Frédéric, Amessou, Mohammed, Mohammed, Ludger, Clarkson, Guy J., Lord, Mike (J. Mike), Stephens, David J. and Roberts, Lynne M.. (2008) The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network. Biochemical Journal, Vol.414 (No.3). pp. 471-484. ISSN 0264-6021

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Abstract

The small-molecule inhibitor Exo2 {4-hydroxy-3-methoxy-(5,6,7,8-tetrahydrol[1]benzothieno[2,3-d]pyrimidin-4-yl)hydraz-one benzaldehyde} has been reported to disrupt the Golgi apparatus completely and to stimulate Golgi–ER (endoplasmic reticulum) fusion in mammalian cells, akin to the well-characterized fungal toxin BFA (brefeldin A). It has also been reported that Exo2 does not affect the integrity of the TGN (trans-Golgi network), or the direct retrograde trafficking of the glycolipid-binding cholera toxin from the TGN to the ER lumen. We have examined the effects of BFA and Exo2, and found that both compounds are indistinguishable in their inhibition of anterograde transport and that both reagents significantly disrupt the morphology of the TGN in HeLa and in BS-C-1 cells. However, Exo2, unlike BFA, does not induce tubulation and merging of the TGN and endosomal compartments. Furthermore, and in contrast with its effects on cholera toxin, Exo2 significantly perturbs the delivery of Shiga toxin to the ER. Together, these results suggest that the likely target(s) of Exo2 operate at the level of the TGN, the Golgi and a subset of early endosomes, and thus Exo2 provides a more selective tool than BFA for examining membrane trafficking in mammalian cells.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Membranes (Biology), Golgi apparatus, Endosomes
Journal or Publication Title:	Biochemical Journal
Publisher:	Portland Press
ISSN:	0264-6021
Date:	4 June 2008
Volume:	Vol.414
Number:	No.3
Page Range:	pp. 471-484
Identification Number:	10.1042/BJ20080149
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England), National Institutes of Health (U.S.) (NIH), Medical Research Council (Great Britain) (MRC)
Grant number:	BB/E012450/1 (BBSRC), 080566Z/06/Z (Wellcome), 5U01A1658969-02 (NIH), Non-Clinical Senior Fellowship G117/554 (MRC)
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URI:	http://wrap.warwick.ac.uk/id/eprint/409

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