Present address: Dto. Inmunologìa, primera planta, Hospital de la Princesa, Madrid 28006, Spain.
Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes
Version of Record online: 9 JUL 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Volume 10, Issue 11, pages 2208–2222, November 2008
How to Cite
Bonazzi, M., Veiga, E., Pizarro-Cerdá, J. and Cossart, P. (2008), Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes. Cellular Microbiology, 10: 2208–2222. doi: 10.1111/j.1462-5822.2008.01200.x
- Issue online: 13 OCT 2008
- Version of Record online: 9 JUL 2008
- Received 18 June, 2008; accepted 22 June, 2008.
Listeria monocytogenes surface proteins internalin (Inl)A and InlB interact with the junctional protein E-cadherin and the hepatocyte growth factor (HGF) receptor Met, respectively, on the surface of epithelial cells to mediate bacterial entry. Here we show that InlA triggers two successive E-cadherin post-translational modifications, i.e. the Src-mediated tyrosine phosphorylation of E-cadherin followed by its ubiquitination by the ubiquitin-ligase Hakai. E-cadherin ubiquitination induces the recruitment of clathrin that is required for optimal bacterial internalization. We also show that the initial clustering of E-cadherin at the bacterial entry site requires caveolin, a protein normally involved in clathrin-independent endocytosis. Strikingly clathrin and caveolin are also recruited at the site of entry of E-cadherin-coated sepharose beads and functional experiments demonstrate that these two proteins are required for bead entry. Together these results not only document how the endocytosis machinery is recruited and involved in the internalization of a zippering bacterium, but also strongly suggest a functional link between E-cadherin endocytosis and the formation of adherens junctions in epithelial cells.