Abstract
Interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. Anthrax toxin protective antigen (PA) binds to the cell surface receptor, enters the cell through receptor-mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. As the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action by providing the toxin with a high-affinity binding anchor on the cell membrane and a path of entry into the host cell. ANTXR2 also acts as a molecular clamp by shifting the pH threshold of PA pore formation to a more acidic pH range, which prevents premature pore formation at neutral pH before the toxin reaches the designated intracellular location. Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of ANTXR2 plays an essential role in anthrax toxin action. Here we will review the roles of ANTXR2 in anthrax toxin action, with an emphasis on newly updated knowledge.
Highlights
Tumor endothelial marker 8 (TEM8) was first reported as a gene that is expressed in human tumor endothelium [1], and capillary morphogenesis gene 2 (CMG2) was found to be differentially expressed during capillary morphogenesis in three-dimensional (3D) collagen matrices [2]
Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action
A few months later, after 2001 anthrax attack, tumor endothelial marker 8 (TEM8) was reported as an anthrax toxin receptor [3], being named anthrax toxin receptor 1 (ANTXR1), which was followed by the identification of CMG2 as the second anthrax toxin receptor (ANTXR2) [4]
Summary
Tumor endothelial marker 8 (TEM8) was first reported as a gene that is expressed in human tumor endothelium [1], and capillary morphogenesis gene 2 (CMG2) was found to be differentially expressed during capillary morphogenesis in three-dimensional (3D) collagen matrices [2]. Both TEM8 and CMG2 are ubiquitously expressed type I transmembrane proteins and share ~40% overall sequence homology. Over the past 14 years, intensive research efforts have been spent to investigate the two receptors and a great deal of knowledge has been generated. We provide an updated review of the most recent research progress concerning ANTXR2, the major receptor for anthrax toxin in vivo, in anthrax toxin action
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