Enhanced-Bystander Bioluminescence Resonnance Energy Transfer (eb-BRET)

Eb-BRET signal of the luciferase-tagged angiotensin AT1 receptor. Upon stimulation with angiotensin II, AT1 receptors translocate to the endosome and generate an eb-BRET signal by associating with the endosomal marker rGFP-FYVE.

In the laboratory of Dr. Michel Bouvier, Chief Executive Officer of the Institute for Research in Immunology and Cancer (IRIC) at Université de Montréal (UdeM) and Principal Investigator in the Molecular Pharmacology research unit, a technology has been developed to visualize and quantify G protein-coupled receptor (GPCR) trafficking in live cells. This new technology development capitalizes on the expertise of Dr. Bouvier’s laboratory in the study of GPCRs and his pioneering work in developing bioluminescence resonance energy transfer (BRET) sensors This technological breakthrough opens new avenues to create new bio-sensors to be used in drug discovery and is featured in the prestigious scientific journal Nature Communications.

GPCRs: a key protein family in the control of various biological processes

G protein-coupled receptors, or GPCRs, form a family of proteins that play central roles in controlling biological processes as varied as neurotransmission, metabolism, cell growth, immune and inflammatory responses, olfaction, and vision. GPCRs are therefore primary targets in drug development and they represent the site of action of over one third of prescribed medications.
This new tool designed with the cooperation of the team of Stéphane Laporte, Professor and Director of Research, Division of Endocrinology and Metabolism, McGill University (Drs. Bouvier and Laporte are co-senior authors of the article published in Nature Communication), will lead to a better understanding of the functions of GPCRs and thus the development of more efficient drugs to treat diseases, including cancer.
This latest technology — Enhanced-Bystander Bioluminescence Resonance Energy Transfer (eb-BRET) — is used to follow intracellular trafficking of G protein-coupled receptors (GPCRs), both during the biosynthetic process and the activation stages by monitoring the movement of receptors and accessory proteins to specific organelles inside the cell.

A breakthrough in the study of GPCRs

“It’s the first time that we have access to such a robust and reliable tool for a quantitative approach in the study of these processes inside live cells,” explains Dr. Michel Bouvier. “This discovery is a significant step in the development of new tools leading to a better understanding of cellular communication. These results would not have been possible without the extraordinary work of members of IRIC, and the close partnership with the team of Stéphane Laporte at McGill University. I salute everyone involved in this discovery and in particular Christian Le Gouill who coordinated the biosensor development. Such team work is further proof that we, at IRIC, work closely with many researchers in Canada and across the world to advance knowledge and accelerate new drug discovery.”

Referenced study

Yoon Namkung, Christian Le Gouill, Viktoria Lukashova Hiroyuki Kobayashi, Mireille Hogue, Etienne Khoury, Mideum Song, Michel Bouvier* & Stephane A. Laporte* (2016).

Monitoring G protein-coupled receptor and b-arrestin trafficking in live cells using enhanced bystander BRET.

Nature communications 7, 12178.

*Co-corresponding authors

View abstract and full article

 

About the Institute for Research in Immunology and Cancer

An ultra-modern research hub and training centre located in the heart of the Université de Montreal, the Institute for Research in Immunology and Cancer (IRIC) was created in 2003 to shed light on the mechanisms of cancer and discover new, more effective therapies to counter this disease. IRIC operates according to a model that is unique in Canada. Its innovative approach to research has already led to discoveries that will, over the coming years, have a significant impact on the fight against cancer. For further information

Information

Olivier Dilain
Communication and media relations advisor
Institute for Research in Immunology and Cancer│IRIC
Université de Montréal
olivier.dilain@umontreal.ca 514-343-7283