Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide.
Type-IV-pilus-mediated adhesion of Neisseria meningitidis (also known as meningococcus) to human endothelial cells induces the formation of membrane protrusions leading to bacterial uptake. We have previously shown that these protrusions result from a Rho- and Cdc42-dependent cortical actin polymerization, and from the activation of the ErbB2 tyrosine-kinase receptor and the Src kinase, leading to tyrosine phosphorylation of cortactin. We report here that N. meningitidis mutants expressing a deglycosylated lipo-oligosaccharide are poorly invasive. These mutants show structurally altered actin polymerization. Moreover, although they efficiently recruit and activate ErbB2 and Src, these mutants are defective in the recruitment and phosphorylation of cortactin. We demonstrate that phosphorylated cortactin controls the cortical actin polymerization, which leads to membrane protrusion formation. In addition, we show that cortactin recruitment is dependent on the activation of a phosphoinositide-3-kinase/Rac1-GTPase signalling pathway, which is required for actin polymerization and internalization of N. meningitidis, and is not activated by the mutant strains. Altogether, these results define a new role for the lipo-oligosaccharide in triggering a phosphoinositide-3-kinase/Rac1 signalling required to elicit an efficient uptake of N. meningitidis in non-phagocytic cells.
Lambotin
Mélanie
M
Département de Biologie Cellulaire, Institut Cochin, INSERM U567, CNRS UMR8104, Université Paris 5 - René Descartes, 22 rue Méchain, 75014 Paris, France.
Hoffmann
Isabelle
I
Laran-Chich
Marie-Pierre
MP
Nassif
Xavier
X
Couraud
Pierre Olivier
PO
Bourdoulous
Sandrine
S
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000382:microbiology; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009345:Neisseria meningitidis / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020830:rac1 GTP-Binding Protein; D019061:src-Family Kinases; C023023:lipid-linked oligosaccharides