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Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

The essential function for serum response factor in T-cell development reflects its specific coupling to

Anastasia Mylona1, Robert Nicolas, Diane Maurice

  • 1Transcription Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.

Molecular and Cellular Biology
|November 25, 2010
PubMed

Insights

Serum response factor (SRF) is crucial for thymocyte positive selection and T-cell development. Extracellular signal-regulated kinase (ERK) signaling via ternary complex factors (TCFs) to SRF is essential for these processes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Serum response factor (SRF) is a transcription factor that interacts with coactivators like ternary complex factors (TCFs) and myocardin-related transcription factors (MRTFs).
  • The necessity of coactivator association for SRF's in vivo function and its specific signaling pathway coupling remains largely uninvestigated.

Purpose of the Study:

  • To investigate the in vivo requirement of coactivator association for SRF function.
  • To determine if specific SRF functions are linked to distinct signaling pathways (ERK-TCF or actin-MRTF).

Main Methods:

  • Utilized SRF null thymocytes and expressed wild-type SRF or various SRF mutants.
  • Assessed thymocyte development, including positive selection and T-cell subset development.
  • Employed fusion proteins to restore specific signaling interactions.

Main Results:

  • SRF is essential for thymocyte positive selection and the development of regulatory T (Treg) and NK T cells, but not for early thymocyte development or negative selection.
  • A mutant SRF (SRF.V194E) unable to recruit TCF or MRTF was inactive in vivo, despite target gene recruitment.
  • Restoring ERK-TCF pathway signaling via a fusion protein rescued SRF function in thymocyte development.

Conclusions:

  • Extracellular signal-regulated kinase (ERK) signaling through the TCF pathway to SRF is necessary and sufficient for SRF's role in thymocyte positive selection.
  • This study clarifies the specific coactivator requirements for SRF-mediated thymocyte development.

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