Moreau Team

Team Leader: Christophe Moreau (CNRS, DR2)

INTRODUCTION

The main theme of the team concerns the development of the "Ion Channel-Coupled Receptor" (ICCR) technology by fusion of G-Protein Coupled Receptors (GPCR) with an ion channel (Kir6.2). The binding of ligands (agonists or antagonists) on the GPCR is translated into an electrical signal by the ion channel. This technology offers many advantages: real time measurement, no labeling, signal proportional to the ligand concentration, independence from intracellular signaling pathways, interfaceable with micro- and nano-electronic devices.
More recently, the team is studying olfactory receptors from vertebrates and insects.
Two lines of research are conducted in parallel: 1) understanding the molecular mechanisms by structure-function approaches; 2) developing applications of these membrane proteins as biosensors.

Key Words:

Structure-function relationships of receptors ; Structure-function relationships of channel ; Protein design and engineering ; Methodological developments

Ion Channel-Coupled Receptor (ICCR), G Protein Coupled Receptors (GPCR), Olfacory receptors, Ion channel, Kir6.2, electrophysiology, double-microelectrodes, voltage-clamp, patch-clamp, HiClamp, Xenopus oocytes

Selected articles:

https://www.webofscience.com/wos/author/record/148275

(* corresponding author ; ° equal contribution)

  • Lemel L°, Nieścierowicz K°, García-Fernández MD°, Darré L, Durroux T, Busnelli M, Pezet M, Rébeillé F, Jouhet J, Mouillac B, Domene C, Chini B, Cherezov V, Moreau CJ*. The ligand-bound state of a G protein-coupled receptor stabilizes the interaction of functional cholesterol molecules. J. Lipid Res. 2021 ; 62 : 10059.
  • Highlights : ASBMB today
  • Principalli MA, Lemel L, Rongier A, Godet A-C, Langer K, Revilloud J, Darré L, Domene C, Vivaudou M, Moreau CJ*. Functional Mapping of the N-terminal Arginine Cluster and C-terminal Acidic Residues of Kir6.2 channel Fused to a G Protein-Coupled Receptor. BBA Biomembranes 2017 ; 1859:2144.
  • Moreau CJ*, Revilloud J, Caro LN, Dupuis JP, Trouchet A, Estrada-Mondragón A, Nieścierowicz K, Vivaudou M. Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors. Sci. Rep. 2017 ; 7:41154.
  • Moreau CJ*, Niescierowicz K, Caro L, Revilloud J, Vivaudou M*. Ion channel reporter for monitoring the activity of engineered GPCRs. Methods Enzymol. 2015 ; 556:425-54.
  • Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A, Moreau C, Li X-D, Poitevin F, Vogel H, Nury H. X-ray structure of the mouse serotonin 5-HT3 receptor. Nature. 2014 ; 512:276-81.
  • Niescierowicz K, Caro L, Cherezov V, Vivaudou M, Moreau CJ*. Functional assay for T4 lysozyme-engineered G Protein-Coupled Receptors with an ion channel reporter. Structure. 2014 ; 22:149-55.
  • Caro LN, Moreau CJ, Estrada-Mondragón A, Ernst OP, Vivaudou M. Engineering of an artificial light-modulated potassium channel. PLoS One. 2012 ; 7:e43766.
  • Caro LN, Moreau CJ, Revilloud J, Vivaudou M. β(2)-Adrenergic Ion-Channel Coupled Receptors as Conformational Motion Detectors. PLoS One. 2011, 6:e18226.
  • Moreau C.J*., Dupuis JP., Revilloud J., Arumugam K. and Vivaudou M*. Electrical biosensors engineered by assembly of a potassium channel with G-protein-coupled receptors. Nature Nanotechnology 2008, 3 : 620-625.
  • Moreau C.°, Jacquet H.°, Prost A-L, D’hahan N. and Vivaudou M. The molecular basis of the specificity of action of KATP channel openers. EMBO J., 2000, 19 : 6644-6651.
  • D’hahan N.°, Moreau C.°, Prost A-L, Jacquet H., Alekseev A.E., Terzic A. and Vivaudou M. Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc. Natl. Acad. Sci. USA, 1999, 96 : 12162-12167.

Fundings:

Current:

Past:

  • ERC CoG NANOZ-ONIC 682286 (2015-2022)
  • CNRS MITI (2019-2020)
  • ANSES (2016-2019)