Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes
In this study we analyzed the spatial and temporal distribution of activated EGFR (p-EGFR) using novel quantitative microscopy methods. We found that p-EGFR is not randomly distributed but packaged at constant mean amounts in individual endosomes, resembling intracellular signalling "quanta". A mathematical model of p-EGFR endocytosis developed to explain quanta formation predicted an unexpected link between endosome fusion and EGFR activity. Different growth factors caused specific changes in endosome number and size in various cell systems, including hepatoblasts. Changing the distribution of p-EGFR between endosomes was sufficient to trigger a different cell fate in PC12 cells in response to EGF. We propose that cells perform an analogue-to-digital conversion by clustering signalling receptors in quanta, thus conferring robustness and specificity to signal transduction. The endosomal distribution could therefore be a predictive parameter of the signalling status of the cell. You can read more about this study here.