Converging physiological roles of the anthrax toxin receptors

Abstract

The anthrax toxin receptors—capillary morphogenesis gene 2 (CMG2) and tumor endothelial marker 8 (TEM8)—were identified almost 20 years ago, although few studies have moved beyond their roles as receptors for the anthrax toxins to address their physiological functions. In the last few years, insight into their endogenous roles has come from two rare diseases: hyaline fibromatosis syndrome, caused by mutations in CMG2, and growth retardation, alopecia, pseudo-anodontia, and optic atrophy (GAPO) syndrome, caused by loss-of-function mutations in TEM8. Although CMG2 and TEM8 are highly homologous at the protein level, the difference in disease symptoms points to variations in the physiological roles of the two anthrax receptors. Here, we focus on the similarities between these receptors in their ability to regulate extracellular matrix homeostasis, angiogenesis, cell migration, and skin elasticity. In this way, we shed light on how mutations in these two related proteins cause such seemingly different diseases and we highlight the existing knowledge gaps that could form the focus of future studies.

Targeting hepatocyte growth factor in epithelial–stromal interactions in an in vitro experimental model of human periodontitis

“…Among the upregulated genes, we identified CYR61/CCN1, interacting with several integrins and thus cell–ECM interactions [ 40 ], BAX, involved in apoptosis regulation [ 41 ], and BOC, a member of the immunoglobulin/fibronectin type III repeat family and thus impacting on cell–cell interactions [ 42 ]. With regard to downregulated genes, we identified ANTXR2 and LAMA3, both being implicated in ECM interactions [ 43 , 44 ]. Further, leukotriene B4 receptor was also downregulated, suggesting a potential modification of the inflammatory status [ 45 , 46 ].…”

Latest therapeutic target for gastric cancer: Anthrax toxin receptor 1

“…ANTXR1 was discovered nearly 20 years ago, although few studies have investigated its physiological function beyond its role as a receptor for anthrax toxin[ 6 ]. In the past few years, insights into its endogenous role have come from a rare disease: Growth retardation, alopecia, false missing teeth and optic nerve atrophy syndrome caused by ANTXR1 functional deletion mutations.…”

Lack of evidence for a role of anthrax toxin receptors as surface receptors for collagen VI and for its cleaved off C5 domain (endotrophin)

“…For that purpose, we expressed and purified recombinant murine C5 and the VWA domains of both Antxr1 and Antxr2 in HEK293T cells (Figure 1A). We decided to use the anthrax toxin receptor VWA domains as they are proposed to be the major extracellular ligand-binding regions of the two receptors and known to be sufficient to bind to the anthrax toxin (26,27). In our analysis we included the VWA domain of Antxr2 even if it was proposed that collagen VI binds to this receptor via its collagenous domain (20).…”