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Interactions between the Actin Cytoskeleton and Anthrax Toxin Receptor 1 (ANTXR1)

Interactions Between the Actin Cytoskeleton and Anthrax Toxin Receptor 1 (ANTXR1)

Kristopher M. Garlick, Doctor of Philosophy, 2012, Department of Laboratory Medicine and Pathobiology, University of Toronto

ABSTRACT

Anthrax is caused by the bacterium Bacillus anthracis, which secretes three proteins that assemble to form a toxic complex at the host cell surface. These proteins are known as protective antigen (PA), lethal factor (LF), and edema factor (EF), and together constitute the major virulence factor of the bacterium. PA binds to one of two cell surface receptors, ANTXR1 or ANTXR2, and facilitates the entry of LF and EF into the cell where they exert various toxic activities. Studying anthrax toxin receptor interactions with PA is thus important for understanding anthrax pathogenesis as well as discerning their natural functions in cells. In this thesis I sought to investigate how interactions with intracellular proteins regulate ligand binding by ANTXR1. Previously it was demonstrated that ANTXR1 associates with the actin cytoskeleton, and this association correlated with low levels of PA binding. It was suggested that this interaction is most likely mediated by adaptor proteins. However, in this thesis I demonstrate that the cytoplasmic domain of ANTXR1 binds directly to actin. Further, I provide evidence that this direct link is sufficient to regulate interactions of the receptor with PA ligands. Finally, I demonstrate that it is the interaction with actin filaments, rather than monomers that accounts for the lower PA binding properties of ANTXR1 compared with receptors that do not associate with actin.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/34008
Date11 December 2012
CreatorsGarlick, Kristopher M.
ContributorsMogridge, Jeremy
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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