Mathematical Modeling of Cannabinoid Receptor Type 2 Endocytosis and Trafficking

G-protein coupled receptor (GPCR) sensitization and desensitization, served as mechanisms to turn the system on and off in response to various ligands, involves mainly the endocytosis and trafficking of receptors. In this study, I utilized a mathematical model to investigate the endocytosis and trafficking of cannabinoid receptor type 2 (CB2), a GPCR highly expressed in the immune system. Two published experimental studies have provided some quantitative data demonstrating the time course of receptor phosphorylation, internalization, dephosphorylation, and recycling under various conditions in transfected Chinese Hamster Ovary cells. Based on these datasets, I developed an ordinary differential equation (ODE)-based model with the assumption that ligands regulate receptor endocytosis and trafficking only by affecting the activation of receptors on the cell surface. Fitting of this model to the data using Markov chain Monte Carlo (MCMC) method suggested that receptor constitutive trafficking is a fundamentally different process than the receptor trafficking under ligand treatment. The key difference between the two processes was shown to be the transfer of receptors from sorting endosome to recycling endosome, and the dephosphorylation of internalized receptors. The model was then modified according to this finding, and the subsequent fitting of the revised model showed a good accordance with the data