title: F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse.
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.
authors.affiliation: Servicio de Inmunología, Hospital Universitario de la Princesa, 28006, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pérez-Martínez
authors.forename: Mónica
authors.initials: M
authors.lastname: Gordón-Alonso
authors.forename: José Román
authors.initials: JR
authors.lastname: Cabrero
authors.forename: Marta
authors.initials: M
authors.lastname: Barrero-Villar
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rey
authors.forename: María
authors.initials: M
authors.lastname: Mittelbrunn
authors.forename: Amalia
authors.initials: A
authors.lastname: Lamana
authors.forename: Giulia
authors.initials: G
authors.lastname: Morlino
authors.forename: Carmen
authors.initials: C
authors.lastname: Calabia
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Shirao
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.forename: Esteban
authors.initials: E
authors.lastname: Veiga
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D046912:Multiprotein Complexes / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020239:Receptor Cross-Talk; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D007376:Interleukin-2; D046912:Multiprotein Complexes; D009479:Neuropeptides; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C053386:drebrins