A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum

Article Article scientifique Article A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum eng 1998-02-09 author Abrami Laurence 502416 author Fivaz Marc 87728 author Glauser Pierre Etienne 58170 author Parton Robert author Van Der Goot Grunberg Françoise G. 24466 525-540 10.1083/jcb.140.3.525 0021-9525 <p>In this paper, we have investigated the effects of the pore-forming toxin aerolysin, produced by <i>Aeromonas hydrophila</i>, on mammalian cells. Our data indicate that the protoxin binds to an 80-kD glycosylphosphatidylinositol (GPI)-anchored protein on BHK cells, and that the bound toxin is associated with specialized plasma membrane domains, described as detergent-insoluble microdomains, or cholesterol-glycolipid "rafts". We show that the protoxin is then processed to its mature form by host cell proteases. We propose that the preferential association of the toxin with rafts, through binding to GPI-anchored proteins, is likely to increase the local toxin concentration and thereby promote oligomerization, a step that it is a prerequisite for channel formation. We show that channel formation does not lead to disruption of the plasma membrane but to the selective permeabilization to small ions such as potassium, which causes plasma membrane depolarization. Next we studied the consequences of channel formation on the organization and dynamics of intracellular membranes. Strikingly, we found that the toxin causes dramatic vacuolation of the ER, but does not affect other intracellular compartments. Concomitantly we find that the COPI coat is released from biosynthetic membranes and that biosynthetic transport of newly synthesized transmembrane G protein of vesicular stomatitis virus is inhibited. Our data indicate that binding of proaerolysin to GPI-anchored proteins and processing of the toxin lead to oligomerization and channel formation in the plasma membrane, which in turn causes selective disorganization of early biosynthetic membrane dynamics. </p> Dewey 540 39 Département de biochimie 144 false The Journal of cell biology 140 3 0dc84a86-148c-4939-88c8-180aa8601c5a Article (Published version) Public ABRAMI_TJCB_1998540.pdf 846711 application/pdf CC BY-NC-SA openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum	The Journal of cell biology			1998	119	141

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Glauser, Pierre Etienne