- Meeting ID: 867 6409 6440
- passcode: 149120
13h00 - 13h50 – Chloé Weckel (INRAE Tours)
Spatiotemporal modeling of signaling pathways: impact of endosomal compartmentalization and application to gonadotropin receptors
Cells communicate with each other by sending extra-cellular ligands such as hormones. Once recognized by their receptors at the plasma membrane, those ligands trigger a signaling cascade within the cell. It is now widely recognized that G Protein-Coupled Receptors (GPCR) are able to trigger signaling cascades both at the plasma membrane and, once internalized, from different endosomal compartments. Furthermore, signal kinetics and spatial localization are major determinants of the cellular response to a given stimulus. Receptor trafficking (internalization/recycling/endosomal dynamics) is therefore a key process in signaling pathways, yet often overlooked in theoretical GPCR dynamic models.
In the first part of our study, we developed a new mathematical framework to incorporate receptor trafficking and signal compartmentalization into generic GPCR models. Using a compartmentalized model based on systems of ordinary differential equations (Chemical Reaction Networks), we studied the effects of internalization and recycling on receptor-induced cellular responses. This approach helped us to address two reciprocal questions: (i) How does trafficking influence cellular responses? and (ii) Does cellular response affect trafficking? For the first case, we demonstrated that receptor trafficking can either enhance or reduce pharmacological action of ligands, depending on plasma membrane versus endosomal signaling properties. For the second case, we reveal that signal feedback on receptor trafficking can induce complex phenomena like multi-stability.
In the second part of our study, we applied this theoretical framework to the Follicle-Stimulating Hormone Receptor (FSHR) signaling pathway. By calibrating our model with high-throughput kinetic data, we show how accounting for receptor trafficking improves pharmacological characterization of ligands and advances our understanding of FSHR signaling pathways.
Dernière modification le 13/03/2026