QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 2 August 2005
doi: 10.1242/jcs.02514

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.02514v1 118/16/3805    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lambotin, M. Articles by Bourdoulous, S. Search for Related Content PubMed PubMed Citation Articles by Lambotin, M. Articles by Bourdoulous, S.

Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide

¹ Département de Biologie Cellulaire, Institut Cochin, INSERM U567, CNRS UMR8104, Université Paris 5 – René Descartes, 22 rue Méchain, 75014 Paris, France
² Laboratoire de Microbiologie, INSERM U570, Faculté de Médecine Necker-Enfants, Malades, 156 rue de Vaugirard, 75015 Paris, France

^* Author for correspondence (e-mail: bourdoulous{at}cochin.inserm.fr)

Accepted 26 May 2005

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.

Key words: Cortactin, Rac1, Phosphoinositide-3-kinase, N. meningitidis, Lipo-oligosaccharide, ErbB2

This article has been cited by other articles:

				R. Louwen, A. Heikema, A. van Belkum, A. Ott, M. Gilbert, W. Ang, H. P. Endtz, M. P. Bergman, and E. E. Nieuwenhuis The Sialylated Lipooligosaccharide Outer Core in Campylobacter jejuni Is an Important Determinant for Epithelial Cell Invasion Infect. Immun., October 1, 2008; 76(10): 4431 - 4438. [Abstract] [Full Text] [PDF]

				S. Tehrani, R. Faccio, I. Chandrasekar, F. P. Ross, and J. A. Cooper Cortactin Has an Essential and Specific Role in Osteoclast Actin Assembly Mol. Biol. Cell, July 1, 2006; 17(7): 2882 - 2895. [Abstract] [Full Text] [PDF]

				N. Doulet, E. Donnadieu, M.-P. Laran-Chich, F. Niedergang, X. Nassif, P. O. Couraud, and S. Bourdoulous Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures J. Cell Biol., May 22, 2006; 173(4): 627 - 637. [Abstract] [Full Text] [PDF]