Abstract by Cody Roberts
Sai Lun Lee
Chemistry and Biochemistry
Increased Antiangiogenic Effect of PASSSR through CMG2 Degradation
Capillary morphogenesis gene protein 2 (CMG2) is a known mediator of angiogenesis and a receptor for anthrax toxin. During anthrax intoxication, a subunit of anthrax, protective antigen (PA83), binds CMG2. PA83 is then cleaved by a cell surface furin-like protease to form PA63. Once cleaved, PA63 oligomerizes and forms (PA63) 7. (PA63) 7 is then taken in by endocytosis. As the endosomal pH drops, (PA63) 7 undergoes a conformational change that creates a beta-barrel that extends through the membrane to transmit other toxin subunits into the cytosol. Unlike during anthrax intoxication, how CMG2 mediates angiogenesis is not well understood. An antiangiogenic effect can be induced in vitro and in vivo by treatment with PA83. Because CMG2 is an endocytic receptor, inhibition could be explained by the rate of CMG2 recycling back to the cellular surface. Here we show the effect of recycling on the potency of the antiangiogenic effect of PA83 and a protease-resistant mutant, PASSSR.