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Genetically encoded optical probes for imaging cellular signaling pathways.

Yoshio Umezawa1

  • 1Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. umezawa@chem.s.u-tokyo.ac.jp

Biosensors & Bioelectronics
|April 28, 2005
PubMed
Summary

Genetically encoded probes enable real-time monitoring of cellular signaling in living cells. These tools facilitate drug screening by detecting hormone receptor activity and protein movement in vitro and in vivo.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biotechnology

Background:

  • Intracellular signaling pathways are crucial for cellular function and can be monitored using genetically encoded probes.
  • These probes offer versatile applications in fundamental research and the screening of pharmaceutical or toxicological compounds.
  • Genetically encoded indicators provide a powerful tool for studying cellular responses in real-time.

Purpose of the Study:

  • To review genetically encoded fluorescent and bioluminescent indicators for monitoring intracellular signaling.
  • To highlight the development and application of specific indicators for estrogen and androgen receptor activity.
  • To demonstrate the utility of these probes for drug discovery and toxicological screening.

Main Methods:

  • Development of a genetically encoded fluorescent indicator (SCCoR) for estrogen receptor activity.

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  • Utilizing a genetically encoded bioluminescent indicator for monitoring androgen receptor nuclear trafficking.
  • Employing cell-based assays and in vivo imaging techniques (e.g., charge-coupled device imaging) for quantitative analysis.

    • Main Results:

    • The SCCoR indicator demonstrated high sensitivity in distinguishing estrogen agonists and antagonists in live cells.
    • Ligand-induced translocation of the androgen receptor was quantitatively sensed in vitro, enabling high-throughput screening.
    • Noninvasive in vivo imaging of androgen receptor translocation in mouse brains was achieved.

    Conclusions:

    • Genetically encoded indicators are effective tools for studying hormone receptor signaling and drug screening.
    • These probes facilitate rapid, quantitative analysis of cellular signaling in both in vitro and in vivo models.
    • The described approaches can be extended to develop biosensors for other receptors and diverse signaling pathways.