MOSDER

The physiology of reproduction is controlled by the action of two pituitary hormones, the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH), on their cognate G protein-coupled receptors, FSHR and LHR, expressed at the cell surface of gonad cells. While the Gs protein-mediated signalling pathway is known to account for the majority of biological outcomes, recent advances supported by our preliminary data show that signalling is generated from three distinct cellular compartments including the plasma membrane (PM) and two endocytic compartments: the early endosome (EE) and the very early endosome (VEE). To date, whether the spatial and temporal encoding of signalling results in specific biological outcomes remains elusive. Moreover, limited knowledge is available regarding the exact molecular mechanisms involved in the control of both receptor trafficking and signalling dynamics. Thus, the MOSDER project aims to gain detailed insights on how FSHR and LHR control the biology of reproduction. To do this, the project will determine the signalling dynamics generated from each of the three compartments, analyse their functional consequences at the cellular level, investigate the underlying molecular mechanisms and characterise the properties of new specific FSHR and LHR ligands on their ability to selectively modulate compartmentalised signalling.