The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation.
The dynamic rearrangement of the actin cytoskeleton plays critical roles in T-cell receptor (TCR) signaling and immunological synapse (IS) formation in T cells. Following actin rearrangement in T cells upon TCR stimulation, we found a unique ring-shaped reorganization of actin called the "actin cloud," which was specifically induced by outside-in signals through lymphocyte function-associated antigen-1 (LFA-1) engagement. In T-cell-antigen-presenting cell (APC) interactions, the actin cloud is generated in the absence of antigen and localized at the center of the T-cell-APC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation involves ADAP (adhesion- and degranulation-promoting adaptor protein) phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (JNK) activation, and occurs independent of TCR and its proximal signaling. The formation of the actin cloud lowers the threshold for subsequent T-cell activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a possible platform for LFA-1-mediated costimulatory function for T-cell activation.
Suzuki
Jun-ichiro
J
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan.
Yamasaki
Sho
S
Wu
Jennifer
J
Koretzky
Gary A
GA
Saito
Takashi
T
D008841:Actin Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D000199:Actins / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000235:genetics; D002448:Cell Adhesion; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology; D019169:Jurkat Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D048057:Mitogen-Activated Protein Kinase 10 / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D016827:CD8 Antigens; C106957:FYB1 protein, human; C491468:Fyb protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D048057:Mitogen-Activated Protein Kinase 10; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases