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The MOSDER project (2022-2026, 433kE) is led by Frédéric Jean-Alphonse, in collaboration with the Institute of Functional Genomics of Montpellier.

Recent advances show that G protein-coupled receptor (GPCR) mediated signaling 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 gonadotropin receptors, the follicle-stimulating hormone receptor (FSHR) and the luteinizing hormone receptor (LHR), activate Gs protein-mediated signaling from the cell surface and from several endocytic compartments. However, the role for FSHR and LHR-mediated Gs signaling 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 organization of Gs protein-mediated signaling at the cellular level. Therefore, the project aims i) at determining the signaling dynamics generated from the plasma membrane and endosomes, ii) at deciphering the functional consequences of compartmentalized signaling, iii) at elucidating the molecular mechanisms of receptor trafficking and signaling in each signaling compartment and iv) at characterizing the functional selectivity properties (biased signaling) of new LHR and FSHR ligands to specifically modulate trafficking and signaling.