The cholesterol-dependent cytolysin listeriolysin O aggregates rafts via oligomerization.
The pore-forming toxin listeriolysin O (LLO) is the main virulence factor of Listeria monocytogenes. LLO is known to act as a pseudo cytokine/chemokine, which induces a broad spectrum of host responses that ultimately influences the outcome of listeriosis. In the present study we demonstrate that LLO is a potent aggregator of lipid rafts. LLO was found to aggregate the raft associated molecules GM1, the GPI-anchored proteins CD14 and CD16 as well as the tyrosine kinase Lyn. Abrogation of the cytolytic activity of LLO by cholesterol pretreatment was found not to interfere with LLO's ability to aggregate rafts or trigger tyrosine phosphorylation in cells. However, a monoclonal antibody that blocks the oligomerization of LLO was found to inhibit rafts' aggregation as well as the induction of tyrosine phosphorylation. This implies that rafts aggregation by LLO which is independent of cytolytic activity, is due to the oligomerization of its membrane bound toxin monomers. Thus, LLO most likely induces signalling through the coaggregation of rafts' associated receptors, kinases and adaptors.
Gekara
Nelson O
NO
Molecular Immunology, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany. nge@gbf.de
Jacobs
Thomas
T
Chakraborty
Trinad
T
Weiss
Siegfried
S
D000818:Animals; D001427:Bacterial Toxins; D001704:Biopolymers; D002460:Cell Line; D002784:Cholesterol / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology*; D006460:Hemolysin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D021962:Membrane Microdomains / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D049128:Sphingolipid Activator Proteins / Q000378:metabolism; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D001427:Bacterial Toxins; D001704:Biopolymers; D004792:Enzyme Precursors; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D049128:Sphingolipid Activator Proteins; D014443:Tyrosine; D002784:Cholesterol; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C038705:hlyA protein, Listeria monocytogenes