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  • The EMBO Journal (2002) 21, 560 - 571
  • doi:10.1093/emboj/21.4.560

Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways

Oliver Billker1, Andreas Popp1, Volker Brinkmann1, Gerald Wenig1, Jutta Schneider2,4, Emmanuelle Caron3 and Thomas F. Meyer1

  1. Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Schumannstras zlige 21/22, D-10117 Berlin, Germany
  2. Universität Freiburg, Institut für Immunbiologie, Stefan-Meier-Stras zlige 8, D-79104 Freiburg, Germany
  3. Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
  4. Present address: Institut für Molekulare Medizin und Zellforschung, Breisacher Stras zlige 66, D-79106 Freiburg, Germany

Correspondence to:

Thomas F. Meyer, E-mail: meyer@mpiib-berlin.mpg.de

Received 12 October 2001; Accepted 13 December 2001; Revised 13 December 2001

Opa adhesins of pathogenic Neisseria species target four members of the human carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. CEACAM receptors mediate opsonization-independent phagocytosis of Neisseria gonorrhoeae by human granulocytes and each receptor individually can mediate gonococcal invasion of epithelial cells. We show here that gonococcal internalization occurs by distinct mechanisms depending on the CEACAM receptor expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen-directed reorganization of the actin cytoskeleton is not required. In marked contrast, ligation of CEACAM3 triggers a dramatic but localized reorganization of the host cell surface leading to highly efficient engulfment of bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho. Two tyrosine residues of a cytoplasmic immune receptor tyrosine-based activating motif of CEACAM3 are essential for the induction of phagocytic actin structures and subsequent gonococcal internalization. The granulocyte-specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM-binding pathogens that colonize human mucosal surfaces.

  • Keywords:

    • carcinoembryonic antigen-related cellular adhesion molecules,
    • Cdc42,
    • invasion,
    • phagocytosis,
    • Rac1