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Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module

Jared E Toettcher1, Orion D Weiner, Wendell A Lim

  • 1Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158-2517, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-2517, USA; Department of Biochemistry, University of California San Francisco, San Francisco, CA 94158-2517, USA.

Cell
|December 10, 2013
PubMed

Insights

Researchers used optogenetics to precisely control cell signaling pathways, revealing how the Ras-Erk pathway transmits information and generates distinct cellular outcomes based on signal timing. This method enhances understanding of complex cell communication. Keywords: optogenetics, cell signaling, Ras-Erk pathway, cellular outcomes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Systems Biology

Background:

  • Cell-signaling networks are complex, making it difficult to understand how cells interpret external cues.
  • The Ras protein is a key node in many signaling pathways that control cell behavior.

Purpose of the Study:

  • To develop and apply an optogenetic method for dissecting intracellular signaling pathways.
  • To characterize signal transmission from Ras to Erk in single cells.
  • To identify how dynamic signaling patterns lead to distinct cellular responses.

Main Methods:

  • Developed an optogenetic system for light-induced activation of specific intracellular signaling nodes.
  • Measured dose- and frequency-response dynamics of the Ras-Erk pathway in single cells.
  • Combined optogenetic stimulation with temporal pattern analysis and proteomic profiling.

Main Results:

  • Characterized the precision, timing, and efficiency of signal flow from Ras to Erk.
  • Identified distinct signaling programs that respond to different Ras activation dynamics.
  • Discovered a paracrine circuit where persistent Ras activation (>1 hr) specifically activates STAT3.

Conclusions:

  • Optogenetic stimulation is a powerful tool for analyzing pathway module transmission properties.
  • Dynamic signaling patterns encode distinct physiological outcomes.
  • This approach provides new insights into cellular decision-making processes.

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