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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7317
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pubmed:dateCreated |
2010-10-14
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pubmed:abstractText |
Bacillus anthracis is the causative agent of anthrax in humans and other mammals. In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mitogen-activated protein-kinase kinases) and EF (cAMP-dependent processes) have been implicated in the initial phase of anthrax, less is understood about toxin action during the final stage of infection. Here we use Drosophila melanogaster to identify the Rab11/Sec15 exocyst, which acts at the last step of endocytic recycling, as a novel target of both EF and LF. EF reduces levels of apically localized Rab11 and indirectly blocks vesicle formation by its binding partner and effector Sec15 (Sec15-GFP), whereas LF acts more directly to reduce Sec15-GFP vesicles. Convergent effects of EF and LF on Rab11/Sec15 inhibit expression of and signalling by the Notch ligand Delta and reduce DE-cadherin levels at adherens junctions. In human endothelial cells, the two toxins act in a conserved fashion to block formation of Sec15 vesicles, inhibit Notch signalling, and reduce cadherin expression at adherens junctions. This coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during B. anthracis infection.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Bacterial,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EXOC6B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Sec15 protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/anthrax toxin,
http://linkedlifedata.com/resource/pubmed/chemical/notch protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/rab GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rab11 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1476-4687
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
467
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
854-8
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pubmed:dateRevised |
2011-10-18
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pubmed:meshHeading |
pubmed-meshheading:20944747-Adherens Junctions,
pubmed-meshheading:20944747-Animals,
pubmed-meshheading:20944747-Antigens, Bacterial,
pubmed-meshheading:20944747-Bacillus anthracis,
pubmed-meshheading:20944747-Bacterial Toxins,
pubmed-meshheading:20944747-Cadherins,
pubmed-meshheading:20944747-Cell Line,
pubmed-meshheading:20944747-Drosophila Proteins,
pubmed-meshheading:20944747-Drosophila melanogaster,
pubmed-meshheading:20944747-Drug Synergism,
pubmed-meshheading:20944747-Endocytosis,
pubmed-meshheading:20944747-Endothelial Cells,
pubmed-meshheading:20944747-Female,
pubmed-meshheading:20944747-GTP-Binding Proteins,
pubmed-meshheading:20944747-Humans,
pubmed-meshheading:20944747-Models, Animal,
pubmed-meshheading:20944747-Protein Binding,
pubmed-meshheading:20944747-Receptors, Notch,
pubmed-meshheading:20944747-Signal Transduction,
pubmed-meshheading:20944747-Transport Vesicles,
pubmed-meshheading:20944747-Vesicular Transport Proteins,
pubmed-meshheading:20944747-rab GTP-Binding Proteins
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pubmed:year |
2010
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pubmed:articleTitle |
Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst.
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pubmed:affiliation |
Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0349, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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