Surface dynamics of aerolysin on the plasma membrane of living cells

Aerolysin secreted by the human pathogen Aeromonas hydrophila belongs to a group of bacterial toxins that are hemolytic and form channels in biologica l membranes. The toxin is secreted as an inactive precursor proaerolysin th at must be proteolytically processed at its C-terminus to become active. Th e toxin then polymerizes into a heptameric ring that is amphipathic and can insert into a lipid bilayer and form a pore. We have examined these variou s steps at the surface of target cells. The toxin binds to specific recepto rs. Various receptors have been identified, all of which are anchored to th e plasma membrane via a glycosylphosphatidyl inositol (GPI)-anchored moiety . The GPI anchor confers to the protein that is linked to it two usual prop erties: (i) the protein has a higher lateral mobility in a phospholipid bil ayer than its transmembrane counterpart, (ii) the protein has the capacity to transiently associate with cholesterol-glycosphingolipid-rich microdomai ns. We have shown that both these properties of GPI-anchored proteins are e xploited by proaerolysin bound to its receptor. The high lateral mobility w ithin the phosphoglyceride region of the plasma membrane favors the encount er of the protoxin with its converting enzyme furin. The ability to associa te with microdomains on the other hand favors the oligomerization process p resumably by concentrating the toxin locally.