Abstract

Capillary Morphogenesis Gene 2 protein (CMG2) is a type 1 transmembrane receptor known as the anthrax toxin receptor 2 (ANTXR2). While it is documented that the cell surface receptor CMG2 mediates anthrax toxin entry into the cell via endocytosis, the physiological role of CMG2 is not well understood. Others have suggested that CMG2 may have a role in mediating ECM homeostasis and angiogenesis. Additionally, both anthrax protective antigen (PA) and a furin protease-resistant mutant, PASSSR, inhibit corneal neovascularization in a mouse model, and interestingly PASSSR has a greater affinity to CMG2 receptor. PASSSRalso has a more potent antiangiogenic effect than wild-type PA. However, a mechanism for PASSSR inhibition of the putative CMG2 role in angiogenesis is not yet elucidated. The experimental results in this thesis provide evidence that CMG2 is the key receptor for regulating adhesion, migration, and actin dynamics in cells, and 200-pM PASSSR inhibits cell adhesion, migration, and actin localization at the cell leading edge. Furthermore, we observed that PASSSR remains bound to CMG2 under acidic conditions similar to the lysosome (pH 4). This observation suggests that the PASSSR-CMG2 complex remains intact following internalization and traffic to lysosomes, different from previous reports for PA, which likely results in CMG2 recycling. Together, these results suggest that following PASSSR treatment, CMG2 traffics to the lysosome for degradation; hence, we predict fewer CMG2 receptors are available at the cell surface to function in their native role in signaling angiogenic processes such as adhesion and chemotaxis towards vascular growth factors.

Degree

MS

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2022-04-15

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd12121

Keywords

Angiogenesis, CMG2, Cell Adhesion, Cell migration, Actin dynamics

Language

english

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