Cell Shape Modulates Information Flow in Signaling Networks

In this talk I will review the consequences of spatially restricted signaling and present an overview of how information content in cell shape is recognized and interpreted by biochemical signaling networks within the cell. My colleagues and I have used a combination of partial differential equation based models and live cell imaging to study the relationships between cell shape and the dynamics of cell signaling networks. These studies indicate that local shape that alter reaction-diffusion kinetics and the negative regulators of signaling such as phosphatases and phosphodiesterases together control information flow to produce local elevations of activated signaling molecules that are called microdomains. A surprising finding from these studies is that information regarding the spatial characteristics of microdomains can be transmitted separately from information regarding activity state of signaling molecules. When signals originate at the cell surface membrane the relative position of intracellular organelles such as the endoplasmic reticulum to the plasma membrane and the presence of negative regulators on the endoplasmic reticulum are both required for the optimization of signaling microdomains in the juxtamembrane region. Recent theoretical studies indicate that the varying shape of cells such as round vs. elongated (fusiform) can regulate transmembrane signaling due to the transient asymmetric accumulation of ligand receptor complexes in the plasma membrane. Thus cell shape interacts with a range of other cellular characteristics to regulate the dynamics of signaling.