Through the action of vacuolar ATPase the pH of the target cell early endosome is lowered. In this environment, paga (PA63, Anthrax protective antigen, large fragment) dissociates from its receptor and forms an oligomeric channel in the endosome membrane through which the anthrax cya (EF, edema factor) and lef (LF, lethal factor) pass (Milne et al. 1994). Entry of cya and lef into the target cell cytosol is thought to be mediated by back fusion of intraluminal vesicles with the late endosomal membrane and to be positively regulated by PDCD6IP / ALIX protein (Abrami et al. 2004).