Membrane Insertion of Anthrax Protective Antigen and Cytoplasmic Delivery of Lethal Factor Occur at Different Stages of the Endocytic Pathway

• Published in: The Journal of cell biology Vol. 166; no. 5; pp. 645 - 651
• Main Authors: Abrami, Laurence, Lindsay, Margaret, Parton, Robert G., Leppla, Stephen H., van der Goot, F. Gisou
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 30.08.2004; The Rockefeller University Press
• Subjects: Animals; Anthrax; Anthrax - metabolism; Antibodies; Antigens; Antigens, Bacterial - metabolism; Antigens, Bacterial - pharmacology; Bacillus anthracis; Bacterial Toxins - metabolism; Bacterial Toxins - pharmacology; Binding sites; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cell membranes; CHO Cells; COP-Coated Vesicles; Cricetinae; Cytoplasm; Cytoplasm - metabolism; Cytoplasm - ultrastructure; Endocytosis - physiology; Endosomes; Endothelial cells; HeLa Cells; Humans; MAP Kinase Kinase 1; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Membranes; Microscopy, Electron; Mitogen-Activated Protein Kinase Kinases - drug effects; Mitogen-Activated Protein Kinase Kinases - metabolism; Protein Subunits - metabolism; rab GTP-Binding Proteins; Toxins; Transport Vesicles - metabolism; Transport Vesicles - ultrastructure; Vacuolar Proton-Translocating ATPases - metabolism; Western blotting
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200312072

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.