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Research ArticleMinireview

A Perspective on Studying GPCR Signaling with RET Biosensors in Living Organisms

Jakobus van Unen, Jeanette Woolard, Ago Rinken, Carsten Hoffmann, Steve Hill, Joachim Goedhart, Michael Bruchas, Michel Bouvier and Merel Adjobo-Hermans
Molecular Pharmacology May 13, 2015, mol.115.098897; DOI: https://doi.org/10.1124/mol.115.098897
Jakobus van Unen
1 University of Amsterdam;
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Jeanette Woolard
2 University of Nottingham;
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Ago Rinken
3 University of Tartu;
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Carsten Hoffmann
4 University of Wurzburg;
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Steve Hill
2 University of Nottingham;
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Joachim Goedhart
1 University of Amsterdam;
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Michael Bruchas
5 Washington University;
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Michel Bouvier
6 Universite de Montreal;
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Merel Adjobo-Hermans
7 Radboud University Medical Center
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Abstract

The last frontier for a complete understanding of G-protein-coupled receptor (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling in vivo, in real time within biologically intact systems. This includes the ability to detect GPCR trafficking, dimerization, protein-protein interactions and receptor activity dynamically, with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)-based biosensors allow for all of these possibilities in vitro, however, moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms as well as the multidisciplinary development of in vitro assays that are more appropriate representatives of the physiological situation. In short, further development of RET-based probes, optical microscopy techniques and mouse genome editing hold great potential over the next decade to bring in vivo real-time GPCR imaging to the forefront of pharmacology.

  • Fluorescence techniques
  • Imaging with fluorescent indicators (e.g. Ca2+ imaging)
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Molecular Pharmacology: 103 (2)
Molecular Pharmacology
Vol. 103, Issue 2
1 Feb 2023
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Research ArticleMinireview

A Perspective on Studying GPCR Signaling with RET Biosensors in Living Organisms

Jakobus van Unen, Jeanette Woolard, Ago Rinken, Carsten Hoffmann, Steve Hill, Joachim Goedhart, Michael Bruchas, Michel Bouvier and Merel Adjobo-Hermans
Molecular Pharmacology May 13, 2015, mol.115.098897; DOI: https://doi.org/10.1124/mol.115.098897

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Research ArticleMinireview

A Perspective on Studying GPCR Signaling with RET Biosensors in Living Organisms

Jakobus van Unen, Jeanette Woolard, Ago Rinken, Carsten Hoffmann, Steve Hill, Joachim Goedhart, Michael Bruchas, Michel Bouvier and Merel Adjobo-Hermans
Molecular Pharmacology May 13, 2015, mol.115.098897; DOI: https://doi.org/10.1124/mol.115.098897
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