Critical roles of plasma membrane dynamics and heterogeneity at the early stage of antigen-stimulated FcεRI signaling in mast cells

Stimulated transmembrane (TM) signaling mediated by plasma membrane localized receptors is central to numerous cellular processes, and their dysregulation leads to pathological conditions. Antigen (Ag) stimulated clustering of high-affinity immunoglobulin E (IgE) receptor FcεRI and its functional coupling of selective signaling components such as kinases, but not phosphatases, in the early stage of mast cell signaling represents the general paradigm of TM signaling mediated by membrane receptors lacking kinase module. It has been long thought that plasma membrane organizational features, especially ordered regions and cortical cytoskeletons network, play crucial roles in efficient spatial sorting of the signaling components. In this review, we highlight the observations made by advanced imaging and spectroscopy techniques at high spatial and temporal resolution that essentially establish novel principles of plasma membrane 'adaptivity' in regulating the initial steps of stimulated mast cell signaling involving Ag cross-linked IgE-FcεRI receptor.