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A general approach for engineering RTKs optically controlled with far-red light.

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Scientists engineered optically controlled receptor tyrosine kinases (RTKs) using far-red light for precise cell signaling studies. This breakthrough enables advanced all-optical assays and in vivo neural activity modulation.

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Area of Science:

  • Cell Biology
  • Neuroscience
  • Biotechnology

Background:

  • Receptor tyrosine kinase (RTK) activity is crucial for understanding cell signaling in biological processes and diseases.
  • Controlling RTK activity is essential for precise manipulation of cellular pathways.

Purpose of the Study:

  • To develop a generalized method for engineering optically controllable RTKs using far-red light.
  • To create a toolkit of engineered RTKs (eDrRTKs) for advanced cell signaling research and in vivo applications.

Main Methods:

  • Engineered cell surface constructs by fusing bacterial phytochrome (DrBphP) to intracellular RTK domains via transmembrane helices.
  • Systematically optimized constructs for various RTKs, including EGFR, HER2, TrkA, TrkB, FGFR1, IR1, cKIT, and cMet.
  • Validated eDrRTK function in mammalian cells and in vivo using far-red light stimulation.

Main Results:

  • Successfully generated optically regulated RTKs (eDrRTKs) responsive to far-red light.
  • Demonstrated rapid induction of downstream signaling in mammalian cells within seconds.
  • Achieved spectral multiplexing with fluorescent probes for all-optical assays.
  • Validated eDrTrkB in mice, showing light-induced neural activity, gene expression, and altered sleep patterns via minimally invasive stimulation.

Conclusions:

  • Developed a versatile platform for optical control of RTKs, enabling precise spatiotemporal manipulation of cell signaling.
  • Established eDrRTKs as powerful tools for all-optical assays and in vivo neuroscience research.
  • Highlighted the potential of far-red light-activated systems for minimally invasive biological research and therapeutic applications.