Spatio-Temporal Signaling in Mast Cells

This chapter summarizes the evidence for localized signaling domains in mast cells and basophils, with a particular focus on the high affinity IgE receptor, FceRI, and its crosstalk with other membrane proteins. It is noteworthy that a literature spanning 30 years established the FceRI as a model receptor for studying activation-induced changes in receptor diffusion and lipid raft association. Now a combination of high resolution microscopy methods, including immunoelectron microscopy and sophisticated fluorescence-based techniques, provide new insight into the nanoscale spatial and temporal aspects of receptor topography on the mast cell plasma membrane. Physical crosslinking of FceRI with multivalent ligands leads to formation of IgE receptor clusters, termed “signaling patches,” that recruit downstream signaling molecules. However, classes of receptors that engage solely with monovalent ligands can also form distinctive signaling patches. The dynamic relationships between receptor diffusion, aggregation state, clustering, signal initiation and signal strength are discussed in the context of these recent findings.