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 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.
Pérez-Martínez
Manuel
M
Servicio de Inmunología, Hospital Universitario de la Princesa, 28006, Madrid, Spain.
Gordón-Alonso
Mónica
M
Cabrero
José Román
JR
Barrero-Villar
Marta
M
Rey
Mercedes
M
Mittelbrunn
María
M
Lamana
Amalia
A
Morlino
Giulia
G
Calabia
Carmen
C
Yamazaki
Hiroyuki
H
Shirao
Tomoaki
T
Vázquez
Jesús
J
González-Amaro
Roberto
R
Veiga
Esteban
E
Sánchez-Madrid
Francisco
F
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
D000199:Actins; D007376:Interleukin-2; D046912:Multiprotein Complexes; D009479:Neuropeptides; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C053386:drebrins