Zooming In and Out on Cellular Signaling mediated by IgE-Receptors

Cells respond to their physical environment and to chemical stimuli in terms of collective molecular interactions that are regulated in time and space. Small molecules may engage specific receptors to initiate a transmembrane signal, and the system amplifies this nanoscale interaction to microscale assemblies within the cell and often to longer length scales involving  surrounding tissue and ultimately the whole organism. A striking example of signal integration over multiple length scales is the allergic immune response. IgE receptors (FcRI) on mast cells are the gatekeepers of this response, and this system has proven to be a valuable model for investigating receptor-mediated cellular activation. Spanning the range of cellular responses we use super resolution fluorescence localization microscopy to investigate the earliest signaling events and ligands patterned in micron size features together with confocal microscopy to investigate early and later events. We are characterizing distinctive regulatory roles played by the actin cytoskeleton at different stages. We are further investigating spatial redistributions of the cellular integrins that relate to the enhancement of signaling observed for cells spreading on surfaces.