Curvature regulates subcellular organelle location to control intracellular signal propagation

The shape of cell is intimately connected to its function; however, we do not fully understand the underlying mechanism by which global shape regulates cell functions. Here, using a combination of theory, experiments and simulation, we investigated how global cell curvature can affect numerous subcellular activities and organization to control signal flow needed for phenotypic function. We find that global cell curvature regulates organelle location, inter-organelle distances and differential distribution of receptors in the plasma membrane. A combination of these factors leads to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCβ pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm and the nucleus as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell curvature affects subcellular organization and signaling to enable expression of phenotype.