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 biological membranes. The toxin is secreted as an inactive precursor proaerolysin that must be proteolytically processed at its C-terminus to become active. The 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 various steps at the surface of target cells. The toxin binds to specific receptors. Various receptors have been identified, all of which are anchored to the plasma membrane via a glycosylphosphatidyl inositol (GPI)-anchored moiety. The GPI anchor confers to the protein that is linked to it two usual properties: (i) the protein has a higher lateral mobility in a phospholipid bilayer than its transmembrane counterpart, (ii) the protein has the capacity to transiently associate with cholesterol-glycosphingolipid-rich microdomains. We have shown that both these properties of GPI-anchored proteins are exploited by proaerolysin bound to its receptor. The high lateral mobility within the phosphoglyceride region of the plasma membrane favors the encounter of the protoxin with its converting enzyme furin. The ability to associate with microdomains on the other hand favors the oligomerization process presumably by concentrating the toxin locally.
Abrami
L
L
Département de Biochimie, Université de Genève, Switzerland.
Fivaz
M
M
van der Goot
F G
FG
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins
D001427:Bacterial Toxins; D017261:Glycosylphosphatidylinositols; D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D052899:Pore Forming Cytotoxic Proteins; C032676:aerolysin