Discs large (Dlg1) complexes in lymphocyte activation

Abstract

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.

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

“…As reported for the neural synapse, other PDZ-containing proteins distinct from syntenin-1 may play a role at the IS. Indeed, it has been reported recently that discs large is recruited to cortical actin in T cell, forms complexes with early participants in the signaling process, and functions as a negative regulator of T cell activation (67).…”

The Ca2+-activated K+ channel KCa3.1 compartmentalizes in the immunological synapse of human T lymphocytes

“…T cell activation. Transfected T cells were stimulated with 4.5-m polystyrene beads coated with anti-CD3/CD28 antibodies (Dynal Biotech, Lake Success, NY) as previously described (30). Transfected T lymphocytes were mixed with the beads at a ratio of 1:1.5 and centrifuged for 5 min at 100 g. The cells were then incubated at 37°C for 30 min, resuspended, and plated onto poly-L-lysine (SigmaAldrich)-coated coverslips and allowed to attach for 3-5 min.…”

DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell–cell contact

“…Since a GFP-tagged human version of hDLG1 expressed at an extremely low level in HeLa cells, we used a GFP-tagged rat DLG1 (rDLG1) to perform immunostaining analysis since this construct gives robust signal for immunofluorescence experiments as previously reported [18,19]. HeLa cells co-transfected with empty Flag vector and rDLG1-GFP showed bright green fluorescence, with a concentration of rDLG1-GFP signal at sites of cell-cell contacts, consistent with previously published results [20,21] (Figure 5A).…”