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Discs large (Dlg1) complexes in lymphocyte activation

Ramnik Xavier1, Shahrooz Rabizadeh, Kazuhiro Ishiguro

  • 1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.

The Journal of Cell Biology
|July 21, 2004
PubMed

Insights

Discs large (Dlg1) protein is recruited to T cell activation sites. Dlg1 regulates T cell receptor signaling, with its reduction enhancing activation, suggesting a role in attenuating immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell activation relies on a structured interface for signal transmission.
  • The molecular mechanisms organizing T cell signaling machinery are not fully understood.

Purpose of the Study:

  • To investigate the role of Discs large (Dlg1) protein in T cell activation.
  • To elucidate the function of Dlg1 in regulating T cell receptor signaling pathways.

Main Methods:

  • Recruitment of Dlg1 to cortical actin upon T cell activation.
  • Analysis of Dlg1 complex formation with early signaling molecules.
  • Overexpression and RNA interference studies to assess Dlg1 function.
  • Measurement of NFAT reporter activation and T cell-mediated signaling.

Main Results:

  • Dlg1 is recruited to cortical actin during T cell activation and forms complexes with signaling molecules.
  • Dlg1 overexpression attenuates basal and Vav1-induced NFAT reporter activation.
  • Reduced Dlg1 expression enhances CD3- and superantigen-mediated NFAT activation.
  • Antigen receptor signaling attenuation involves segregation of early signaling complex elements.

Conclusions:

  • Dlg1 plays a critical role in regulating T cell activation.
  • Dlg1 functions to attenuate T cell receptor signaling.
  • The findings highlight the complex, orchestrated nature of T cell signaling attenuation.

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