Experiments using fluorescent reporters have shown that the spatial distribution of many signaling pathway components is altered following a change in the chemoattractant cAMP concentration. These changes occur during the first 0-10 sec after binding or unbinding of the ligand to the receptors. Within this time frame, the membrane closest to the cAMP source experiences an increase in certain signaling components while other components display an increased concentration at the membrane away from the source. Even though a large number of signaling components have been identified, the precise mechanisms of directional sensing remain unclear. To fully understand these mechanisms it is essential to obtain quantitative data using precisely controlled stimulations. To address these mechanisms, we propose to investigate the initial phase of the chemotaxis process using an approach in which the chemoattractant stimulus can be carefully controlled, both spatially and temporally. The results from these experiments will be integrated into models that, in turn, will guide the experiments. We believe that such interaction of modeling with experimentation is essential for making progress in understanding eukaryotic chemotaxis. Indeed, it is this interaction that has proven to be fruitful during the past 4 years.
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