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ARHGAP10 is necessary for α-catenin recruitment at adherens junctions and for Listeria invasion

Nature Cell Biology volume 7, pages 954960 (2005) | Download Citation

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Abstract

E-cadherin mediates the formation of adherens junctions between epithelial cells1. It serves as a receptor for Listeria monocytogenes, a bacterial pathogen that enters epithelial cells2. The L. monocytogenes surface protein, InlA, interacts with the extracellular domain of E-cadherin3,4,5. In adherens junctions, this ectodomain is involved in homophilic interactions whereas the cytoplasmic domain binds β-catenin, which then recruits α-catenin. α-catenin binds to actin directly, or indirectly, thus linking E-cadherin to the actin cytoskeleton6,7. Entry of L. monocytogenes into cells and adherens junction formation are dynamic events that involve actin and membrane rearrangements. To understand these processes better, we searched for new ligands of α-catenin. Using a two-hybrid screen, we identified a new partner of α-catenin: ARHGAP10. This protein colocalized with α-catenin at cell–cell junctions and was recruited at L. monocytogenes entry sites. In ARHGAP10-knockdown cells, L. monocytogenes entry and α-catenin recruitment at cell–cell contacts were impaired. The GAP domain of ARHGAP10 has GAP activity for RhoA and Cdc42. Its overexpression disrupted actin cables, enhanced α-catenin and cortical actin levels at cell–cell junctions and inhibited L. monocytogenes entry. Altogether, our results show that ARHGAP10 is a new component of cell–cell junctions that controls α-catenin recruitment and has a key role during L. monocytogenes uptake.

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Acknowledgements

We thank Dr. A. Hall for the generous gift of p50-RhoGAP purified protein, members of P. Cossart's laboratory for helpful discussions and Hybrigenics staff for their contributions. This work received financial support from Institut Pasteur (GPH N°9); French Ministry of Research (Programme de Microbiologie Fondamentale et Apliquée, Maladies Infectieuses, Environment et Bioterrorisme ACI N° MIC 0312) and Association pour la Recherche sur le Cancer (ARC4404). S. Sousa is a recipient of a Fellowship from the Portuguese Government (SFRH/BD/1374/2000 and POCTI-LA000308-BPD). P. Cossart is an International Research Scholar of the Howard Hughes Medical Institute.

Author information

Author notes

    • Sandra Sousa
    •  & Didier Cabanes

    Present addresses: Institute for Molecular and Cell Biology, Molecular Microbiology, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;

Affiliations

  1. Unité des Interactions Bactéries-Cellules Institut Pasteur, INSERM U604, INRA USC2020, 28 Rue du Dr Roux, 75724 Paris Cedex 15, France.

    • Sandra Sousa
    • , Didier Cabanes
    • , Cristel Archambaud
    • , Stéphanie Boisson-Dupuis
    • , Edith Gouin
    • , Marc Lecuit
    •  & Pascale Cossart
  2. Hybrigenics SA, 3-5 Impasse Reille, 75014 Paris, France.

    • Frédéric Colland
  3. Bacterial toxins in host-pathogen interaction, Faculté de Médecine de Nice, 28 Avenue de Valombrose, Nice 06107 Cedex 02, France.

    • Emmanuel Lemichez
    •  & Pierre Legrain
  4. Unité Bacteries anaerobies et Toxines Institut Pasteur, Paris.

    • Michel Popoff
  5. Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.

    • Marc Lecuit
  6. Département de Biologie Joliot-Curie, CEA, 91191 Gif-sur-Yvette CEDEX, France.

    • Pierre Legrain

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Pascale Cossart.

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DOI

https://doi.org/10.1038/ncb1308

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