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ERM proteins regulate cytoskeleton relaxation promoting T cell–APC conjugation

Nature Immunology volume 5, pages 272–279 (2004)Cite this article

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Abstract

During activation, T cells associate with antigen-presenting cells, a dynamic process that involves the formation of a broad area of intimate membrane contact known as the immunological synapse. The molecular intermediates that link initial antigen recognition to the cytoskeletal changes involved in this phenomenon have not yet been defined. Here we demonstrate that ezrin-radixin-moesin proteins are rapidly inactivated after antigen recognition through a Vav1-Rac1 pathway. The resulting disanchoring of the cortical actin cytoskeleton from the plasma membrane decreased cellular rigidity, leading to more efficient T cell–antigen-presenting cell conjugate formation. These findings identify an antigen-dependent molecular pathway that favors immunological synapse formation and the subsequent development of an effective immune response.

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Figure 1: Human PBT activation results in ERM dephosphorylation.
Figure 2: Effect of Rho GTPases on the phosphorylation of the ERM proteins in human PBTs.
Figure 3: ERM inactivation is Pak1 independent.
Figure 4: Analysis of TCR-mediated ERM inactivation in T lymphocytes from Vav1-deficient mice.
Figure 5: Effect of ERM dominant negative expression on endogenous ERM proteins and the cortical actin cytoskeleton.
Figure 6: Analysis of cellular rigidity.
Figure 7: Effect of (FERM)Ez and Rac1L61 expression on T cell–APC conjugate formation.

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  • 09 February 2004

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Acknowledgements

We thank J.K. Burkhardt, N. Hotchin and A. Hall for providing us with constructs; and S. Shaw, C. Randriamampita and E. Donnadieu for critical reading of the manuscript and suggestions. Supported by Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Ligue Nationale contre le Cancer, Région Ile-de-France and Association Claude Bernard (M.S.).

*Note: In the version of this article originally published online, the labeling of the last two lanes in Figure 2a was incorrect. They should read "GFP-Rac1L61" and "GFP-Cdc42L61." This error has been corrected for the HTML and print versions of the article.

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Authors and Affiliations

  1. Département de Biologie Cellulaire, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U567/Centre National de la Recherche Scientifique UMR 8104, Université René Descartes, 22 rue Méchain, Paris, 75014, France

    Sophie Faure, Monique Semichon, Georges Bismuth, Alain Trautmann & Jérôme Delon

  2. Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, 20892, Maryland, USA

    Laura Inés Salazar-Fontana, Ronald N Germain & Jérôme Delon

  3. Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Victor L J Tybulewicz

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Faure, S., Salazar-Fontana, L., Semichon, M. et al. ERM proteins regulate cytoskeleton relaxation promoting T cell–APC conjugation. Nat Immunol 5, 272–279 (2004). https://doi.org/10.1038/ni1039

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