F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

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 neuron...

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Published inJournal of cell science Vol. 123; no. 7; pp. 1160 - 1170
Main Authors Pérez-Martínez, Manuel, Gordón-Alonso, Mónica, Cabrero, José Román, Barrero-Villar, Marta, Rey, Mercedes, Mittelbrunn, María, Lamana, Amalia, Morlino, Giulia, Calabia, Carmen, Yamazaki, Hiroyuki, Shirao, Tomoaki, Vázquez, Jesús, González-Amaro, Roberto, Veiga, Esteban, Sánchez-Madrid, Francisco
Format Journal Article
LanguageEnglish
Published England The Company of Biologists Limited 01.04.2010
Subjects
Actins - metabolism
Animals
Cytoskeleton - metabolism
Humans
Immunological Synapses - genetics
Immunological Synapses - metabolism
Interleukin-2 - secretion
Jurkat Cells
Lymphocyte Activation - genetics
Multiprotein Complexes - metabolism
Neuropeptides - genetics
Neuropeptides - metabolism
PC12 Cells
Protein Binding
Protein Transport
Rats
Receptor Cross-Talk
Receptors, CXCR4 - metabolism
RNA, Small Interfering - genetics
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
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ISSN0021-9533
1477-9137
1477-9137
DOI10.1242/jcs.064238

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Summary: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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ISSN:0021-9533
1477-9137
1477-9137
DOI:10.1242/jcs.064238