ANR MOSDER

Le projet MOSDER (2022-2026, 433kE) est porté par Frédéric Jean-Alphonse, en collaboration avec l'Institut de Génomique Fonctionnelle de Montpellier.

Recent advances show that G protein-coupled receptor (GPCR) mediated signalling through G protein can be spatially and temporally regulated to achieve specific physiological responses1-3. Previous studies from partner 1 and collaborators indicate that both gonadotrophin receptors, the follicle-stimulating hormone receptor (FSHR) and the luteinizing hormone receptor (LHR), activate Gs protein-mediated signalling from the cell surface and from several endocytic compartments. However, the role for FSHR and LHR-mediated Gs signalling from distinct cellular locations on gonadal physiology remains largely unexplored. We hypothesize that FSHR and LHR signal from distinct cellular compartments to specifically and precisely regulate distinct gonadal functions. Consequently, the objective of the “MOSDER” project is to gain comprehensive knowledge on how FSHR and LHR control reproduction through spatial and temporal organisation of Gs protein-mediated signalling at the cellular level. Therefore, the project aims i) at determining the signalling dynamics generated from the plasma membrane and endosomes, ii) at deciphering the functional consequences of compartmentalised signalling, iii) at elucidating the molecular mechanisms of receptor trafficking and signalling in each signalling compartment and iv) at characterising the functional selectivity properties (biased signalling) of new LHR and FSHR ligands to specifically modulate trafficking and signalling.