Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors

Philipp Leippe1,2, Johannes Broichhagen1,3, Katia Cailliau4

  • 1Department of Chemistry, Ludwig-Maximilians-Universität München and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377, München, Germany.

Insights

Scientists engineered human receptors to respond to light and glutamate, creating novel light-controlled signaling pathways. This breakthrough offers a new method for controlling cellular functions optically.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • Receptor tyrosine kinases (RTKs) are crucial for cellular functions in animals.
  • Typically, vertebrate RTKs are activated by proteins, not amino acids or light.
  • Venus kinase receptors (VKRs) are atypical RTKs offering inspiration for novel receptor engineering.

Purpose of the Study:

  • To engineer human insulin receptor (hIR) and hepatocyte growth factor receptor (hMET) for light and glutamate sensitivity.
  • To develop a general strategy for converting existing RTKs into light-sensitive photoreceptors.

Main Methods:

  • Chimeric receptors were created by replacing extracellular domains of hIR and hMET with the ligand-binding domain of metabotropic glutamate receptor type 2 (mGluR2).
  • Light sensitivity was introduced using a synthetic glutamate-based photoswitch attached via a SNAP tag.
  • Functional assays in Xenopus laevis oocytes were used to measure kinase activity.

Main Results:

  • Successfully generated light-controlled human insulin receptor (LihIR) and light-controlled MET receptor (LihMET).
  • Demonstrated optical control over insulin and MET signaling pathways using these engineered receptors.
  • Validated the potential of this strategy for converting RTKs into photoreceptors.

Conclusions:

  • Engineered RTKs can be converted into light-sensitive receptors with tunable signaling pathways.
  • This approach provides a versatile platform for optical control of cellular processes.
  • The findings open new avenues for research in optogenetics and targeted therapeutics.

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