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Trafficking Coordinate Description of Intracellular Transport Control of Signaling Networks

Many cellular networks rely on the regulated transport of their components to transduce extracellular information into precise intracellular signals. The dynamics of these networks is typically described in terms of compartmentalized chemical reactions. There are many important situations, however, in which the properties of the compartments change continuously in a way that cannot naturally be described by chemical reactions. Here, we develop an approach based on transport along a trafficking coordinate to precisely describe these processes and we apply it explicitly to the TGF-β signal transduction network, which plays a fundamental role in many diseases and cellular processes. The results of this newly introduced approach accurately capture for the first time the distinct TGF-β signaling dynamics of cells with and without cancerous backgrounds and provide an avenue to predict the effects of chemical perturbations in a way that closely recapitulates the observed cellular behavior.