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Published 19 July 2004. doi:10.1083/jcb.200309044
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 2, 173-178
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Reports

 Discs large (Dlg1) complexes in lymphocyte activation

Ramnik Xavier1,2, Shahrooz Rabizadeh1, Kazuhiro Ishiguro2, Niko Andre2, J. Bernabe Ortiz2, Heather Wachtel2, David G. Morris3, Marco Lopez-Ilasaca4, Albert C. Shaw3, Wojciech Swat5, and Brian Seed1

1 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114
2 Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114
3 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520
4 Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115
5 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Address correspondence to Brian Seed, Dept. of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114. Tel.: (617) 726-5975. Fax: (617) 726-5962. email: seed{at}molbio.mgh.harvard.edu

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.

Key Words: Discs large; scaffold protein; PDZ domains; lymphocyte activation

Abbreviations used in this paper: APC, antigen-presenting cell; Dlg1, Discs large; GK, guanylate kinase; MAGUK, membrane-associated guanylate kinase; SEE, staphylococcal enterotoxin E; shRNA, short hairpin RNA; TCR, T cell antigen receptor.


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