Discs Large (Dlg1) Complexes in Lymphocyte Activation

• Published in: The Journal of cell biology Vol. 166; no. 2; pp. 173 - 178
• Main Authors: Xavier, Ramnik, Rabizadeh, Shahrooz, Ishiguro, Kazuhiro, Andre, Niko, Ortiz, J. Bernabe, Wachtel, Heather, Morris, David G., Lopez-Ilasaca, Marco, Shaw, Albert C., Swat, Wojciech, Seed, Brian
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 19.07.2004; The Rockefeller University Press
• Subjects: Actins; Actins - metabolism; Adaptor Proteins, Signal Transducing; Animals; Antibodies; Antigens; B lymphocytes; CD3 Complex - physiology; Cell lines; Cell membranes; Cells; Discs Large Homolog 1 Protein; DNA-Binding Proteins - metabolism; Drosophila; Guanylate Kinases; Humans; Immune system; Jurkat Cells; Lymphocyte Activation; Membrane Proteins; Mice; Mice, Transgenic; Molecules; NFATC Transcription Factors; Nuclear Proteins; Protein Transport; Proteins; Proteins - immunology; Proteins - metabolism; Rats; Signal Transduction; Signaling; Superantigens - pharmacology; T cell antigen receptors; T lymphocytes; T-Lymphocytes - chemistry; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; Transcription Factors - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200309044

T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex.