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Published 1 October 2001. doi:10.1083/jcb.200106148
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© The Rockefeller University Press, 0021-9525/2001/10/133 $5.00
The Journal of Cell Biology, Volume 155, Number 1, October 1, 2001 133-144

Article

 Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial cells by Neisseria meningitidis

Isabelle Hoffmann1, Emmanuel Eugène2, Xavier Nassif2, Pierre-Olivier Couraud1 and Sandrine Bourdoulous1

1 Laboratoire d'Immuno-Pharmacologie Moléculaire, Centre National de la Recherche Scientifique, Institut Cochin de Génétique Moléculaire, 75014 Paris, France
2 Laboratoire de Microbiologie, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Necker-Enfants Malades, 75015 Paris, France

Address correspondence to Sandrine Bourdoulous, Laboratoire d'Immuno-Pharmacologie Moléculaire, Centre National de la Recherche Scientifique UPR 415, Institut Cochin de Génétique Moléculaire, 22 rue Méchain, 75014 Paris, France. Tel.: (33) 1-40-51-64-34. Fax: (33) 1-40-51-64-30. E-mail: bourdoulous{at}cochin.inserm.fr

ErbB2 is a receptor tyrosine kinase belonging to the family of epidermal growth factor (EGF) receptors which is generally involved in cell differentiation, proliferation, and tumor growth, and activated by heterodimerization with the other members of the family. We show here that type IV pilus–mediated adhesion of Neisseria meningitidis onto endothelial cells induces tyrosyl phosphorylation and massive recruitment of ErbB2 underneath the bacterial colonies. However, neither the phosphorylation status nor the cellular localization of the EGF receptors, ErbB3 or ErbB4, were affected in infected cells. ErbB2 phosphorylation induced by N. meningitidis provides docking sites for the kinase src and leads to its subsequent activation. Specific inhibition of either ErbB2 and/or src activity reduces bacterial internalization into endothelial cells without affecting bacteria-induced actin cytoskeleton reorganization or ErbB2 recruitment. Moreover, inhibition of both actin polymerization and the ErbB2/src pathway totally prevents bacterial entry. Altogether, our results provide new insight into ErbB2 function by bringing evidence of a bacteria-induced ErbB2 clustering leading to src kinase phosphorylation and activation. This pathway, in cooperation with the bacteria-induced reorganization of the actin cytoskeleton, is required for the efficient internalization of N. meningitidis into endothelial cells, an essential process enabling this pathogen to cross host cell barriers.

Key Words: ErbB2; homodimerization; src; Neisseria meningitidis; invasion


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