F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse
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2010
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The Company of Biologists
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Manuel Pérez-Martínez, Mónica Gordón-Alonso, José Román Cabrero, Marta Barrero-Villar, Mercedes Rey, María Mittelbrunn, Amalia Lamana, Giulia Morlino, Carmen Calabia, Hiroyuki Yamazaki, Tomoaki Shirao, Jesús Vázquez, Roberto González-Amaro, Esteban Veiga, Francisco Sánchez-Madrid; F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse. J Cell Sci 1 April 2010; 123 (7): 1160–1170. doi: https://doi.org/10.1242/jcs.064238
Abstract
The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding protein. Drebrin colocalizes with the chemokine receptor CXCR4 and F-actin at the peripheral supramolecular activation cluster in the immune synapse. Drebrin interacts with the cytoplasmic tail of CXCR4 and both proteins redistribute to the immune synapse with similar kinetics. Drebrin knockdown in T cells impairs the redistribution of CXCR4 and inhibits actin polymerization at the immune synapse as well as IL-2 production. Our data indicate that drebrin exerts an unexpected and relevant functional role in T cells during the generation of the immune response.
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Acknowledgements
This work was partly supported by EU-México FONCICYT –C002-2008-1 ALA/127249, SAF-2008-02635, INSINET 01592006 CAM, Red RECAVA RD06/0014-0030 and FIPSE 36658/07 grants. E.V.C. holds a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank H. de la Fuente for statistical assistance. Editorial assistance was provided by S. Bartlett. G.M. is supported by the European Union-funded International Graduate Program in Molecular Medicine.