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Lymphocyte migration, which is essential for effective immune responses, belongs to the so-called amoeboid migration. The lymphocyte migration is up to 100 times faster than between mesenchymal and epithelial cell types. Migrating lymphocytes are highly polarized in three well-defined structural and functional zones: uropod, medial zone, and leading edge (LE). The actiomyosin-dependent driving force moves forward the uropod, whereas massive actin rearrangements protruding the cell membrane are observed at the LE. These actin rearrangements resemble those observed at the immunological synapse driven by clathrin, a protein normally involved in endocytic processes. Here, we used cell lines as well as primary lymphocytes to demonstrate that clathrin and clathrin adaptors colocalize with actin at the LE of migrating lymphocytes, but not in other cellular zones that accumulate both clathrin and actin. Moreover, clathrin and clathrin adaptors, including Hrs, the clathrin adaptor for multivesicular bodies, drive local actin accumulation at the LE. Clathrin recruitment at the LE resulted necessary for a complete cell polarization and further lymphocyte migration in both 2D and 3D migration models. Therefore, clathrin, including the clathrin population associated to internal vesicles, controls lymphocyte migration by regulating actin rearrangements occurring at the LE.

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., 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., Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.

El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.