European Conference on Mathematical and Theoretical Biology (ECMTB 2026)

Spatiotemporal modeling of signaling pathways: impact of endosomal compartmentalization and application to gonadotropin receptors

MS105-02

16 Jul 2026, 11:00

20m

11.03 - HS (University of Graz)

Minisymposium Talk Systems Biology and Biochemical Networks Applications of reaction networks

Speaker

Chloe Weckel (BIOS, PRC, UMR CNRS, Université de Tours, INRAE, INRAE Centre Val de Loire 37380 Nouzilly, France / MUSCA, Université Paris-Saclay, Inria, Centre Inria de Saclay, 91120 Palaiseau, France)

Description

Cells communicate by sending extracellular ligands such as hormones. Once recognized by their plasma membrane receptors, these ligands trigger intracellular signaling cascades. G Protein-Coupled Receptors (GPCRs) can activate such cascades both at the plasma membrane and, once internalized, from endosomal compartments. Signal kinetics and spatial organization are key determinants of cellular responses. Receptor trafficking (internalization, recycling, endosomal dynamics) thus plays a crucial role in signaling pathways, yet it remains underexplored in theoretical GPCR models. We developed a mathematical framework incorporating receptor trafficking and signal compartmentalization into generic GPCR models. Using a compartmentalized system of ordinary differential equations, we analyzed how internalization and recycling affect receptor-induced responses. This framework addresses two questions: (i) How does trafficking influence signaling? and (ii) How does signaling feedback affect trafficking? We show that trafficking can enhance or reduce ligand action depending on membrane versus endosomal signaling and that feedback mechanisms can generate multi-stability. Applied to the Follicle-Stimulating Hormone Receptor (FSHR), our model calibrated with kinetic data improves ligand characterization and understanding of FSHR signaling.