IgE Mediated Signaling
|
| Overview Basic molecular mechanisms of cell surface receptors that mediate transmembrane signals can be elucidated by integrating information from multiple interdisciplinary approaches. Our studies focus on the receptor (FceRI) for immunoglobulin E (IgE) that plays a central role in the allergic response and serves as a model for other types of immune receptors. Binding and cross-linking of IgE-FceRI complexes by antigen initiates transmembrane signal transduction resulting in cell activation and release of chemical mediators. We measure kinetics and thermodynamics of binding and cross-linking between cell-bound IgE and structurally defined ligands with fluorescence methods and analyze with realistic theoretical models to determine features that are critical for signaling. Quantitative fluorescence microscopy, including imaging and fluorescence correlation spectroscopy, is used to monitor changes in the distribution and dynamics of the receptor and signaling components (and genetically engineered analogs) that accompany receptor cross-linking and cellular activation. Using biochemical and biophysical approaches we found that IgE receptor-mediated signaling involves plasma membrane domains based on ordered lipids (also known as "lipid rafts") that enable regulation and targeting of the signaling components. Our ongoing collaborative studies apply mass spectrometry and electron microscopy and other powerful analytical methods to investigate the composition, structure and dynamics of the participating membrane components. These are related to stimulated cellular activities such as phosphorylation, Ca2+ mobilization, and membrane trafficking, and degranulation, that are measured in parallel. Together with these other approaches, we are developing nanofabrication technology to probe immunological systems on subcellular and molecular scales. More information about specific projects can be found at the links below: |
Publications · Links