Plasma membrane microdomains act as concentration platforms to facilitate intoxication by aerolysin.
It has been proposed that the plasma membrane of many cell types contains cholesterol-sphingolipid-rich microdomains. Here, we analyze the role of these microdomains in promoting oligomerization of the bacterial pore-forming toxin aerolysin. Aerolysin binds to cells, via glycosyl phosphatidylinositol-anchored receptors, as a hydrophilic soluble protein that must polymerize into an amphipathic ring-like complex to form a pore. We first show that oligomerization can occur at >10(5)-fold lower toxin concentration at the surface of living cells than in solution. Our observations indicate that it is not merely the number of receptors on the target cell that is important for toxin sensitivity, but their ability to associate transiently with detergent resistant microdomains. Oligomerization appears to be promoted by the fact that the toxin bound to its glycosyl phosphatidylinositol-anchored receptors, can be recruited into these microdomains, which act as concentration devices.
Abrami
L
L
Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland.
van Der Goot
F G
FG
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003505:Cyclodextrins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006028:Glycosphingolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007700:Kinetics; D017830:Octoxynol / Q000494:pharmacology; D011108:Polymers; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D012995:Solubility / Q000187:drug effects; D013696:Temperature; D047392:beta-Cyclodextrins
D001427:Bacterial Toxins; D003505:Cyclodextrins; D006028:Glycosphingolipids; D017261:Glycosylphosphatidylinositols; D011108:Polymers; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D012503:Saponins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C107096:proaerolysin; C032676:aerolysin; D017830:Octoxynol; D002784:Cholesterol