Plasma Membrane Heterogeneity and Receptor Mediated Signaling

From Q-bio

The complex role of plasma membrane structure in orchestrating receptor-mediated signal transduction is addressed in collaborative studies investigating how antigen crosslinking of IgE- receptors on mast cells initiates signaling pathways leading to multiple cellular responses. Segregation of liquid ordered regions from disordered regions of the plasma membrane provides protection from transmembrane phosphatases and thereby a mechanism for crosslinking-dependent phosphorylation of IgE-receptors by active Lyn kinase in the first signaling event. Soluble ligands with rigid spacers provide evidence for transphosphorylation as an amplification step and reveal other structural constraints in distinctive signaling pathways. Defined clustering of IgE-receptors with patterned lipid bilayers enables fluorescence visualization of co-redistributing signaling components with spatial resolution on the micron scale, and nanoscale resolution of clustering components is visualized with scanning electron microscopy. Giant plasma membrane vesicles, uncoupled from the cytoskeleton, undergo clear phase separation at low temperatures and can be used to investigate partitioning of lipids and proteins between coexisting fluid phases. These integrated approaches for examining membrane structural heterogeneity and functional consequences will be discussed.