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PMID: 15337774 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway.

The Journal of cell biology ·Vol. 166 ·No. 5 ·2004-08-30 ·Pages 645-51

Abrami L, Lindsay M, Parton RG, Leppla SH, van der Goot FG

Abstract

The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and binds the enzymatic subunits, the lethal factor (LF) and the edema factor (EF). The resulting complex is then endocytosed. Via mechanisms that depend on the vacuolar ATPase and require membrane insertion of PA, LF and EF are ultimately delivered to the cytoplasm where their targets reside. Here, we show that membrane insertion of PA already occurs in early endosomes, possibly only in the multivesicular regions, but that subsequent delivery of LF to the cytoplasm occurs preferentially later in the endocytic pathway and relies on the dynamics of internal vesicles of multivesicular late endosomes.

MeSH Terms
Animals Anthrax/metabolism Antigens, Bacterial/metabolism,pharmacology Bacterial Toxins/metabolism,pharmacology CHO Cells COP-Coated Vesicles Cell Membrane/metabolism,ultrastructure Cricetinae Cytoplasm/metabolism,ultrastructure Endocytosis/physiology HeLa Cells Humans MAP Kinase Kinase 1 MAP Kinase Signaling System/drug effects,physiology Microscopy, Electron Mitogen-Activated Protein Kinase Kinases/drug effects,metabolism Protein Subunits/metabolism Transport Vesicles/metabolism,ultrastructure Vacuolar Proton-Translocating ATPases/metabolism rab GTP-Binding Proteins
Chemicals
Antigens, Bacterial Bacterial Toxins Protein Subunits anthrax toxin MAP Kinase Kinase 1 MAP2K1 protein, human Mitogen-Activated Protein Kinase Kinases Vacuolar Proton-Translocating ATPases rab GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Abrami Laurence
Department of Microbiology and Molecular Medicine, University of Geneva, 1 rue Michel Servet, Geneva, Switzerland 1211.
Lindsay Margaret
Parton Robert G
Leppla Stephen H
van der Goot F Gisou
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200312072
Published
2004-08-30
Pages
645-51
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172425
Subset
IM
Grants
NIAID NIH HHS · R21 AI053270 · United States
NIAID NIH HHS · AI053270-01 · United States
External Links
PubMed source DOI: 10.1083/jcb.200312072 PMC Full Text View journal details
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