Mast cell degranulation – the exocytic release of inflammatory mediators – occurs in response to antigen-mediated crosslinking of cell surface IgE receptors and is important for the inflammatory response. Previous studies have highlighted the importance of oscillatory Ca2+ waves in the exocytosis of these secretory lysosomes, but the spatiotemporal relationship between Ca2+ mobilisation and degranulation are not yet fully understood. Here, Roy Cohen, Barbara Baird and colleagues (p. ) describe a new method to study the exocytic events during degranulation and use this to provide further insights into this process. They illustrate that the pH-sensitive dye FITC–dextran specifically accumulates in secretory lysosomes and can be used to image the exocytic events of individual granules. Using this approach, they reveal that degranulation kinetics depend on mast cell attachment to a substrate: a longer adherence to a substrate correlates with faster degranulation. Furthermore, at limiting antigen concentrations, exocytosis preferentially occurs along cell protrusions, which also form the initiation site of the Ca2+ wave. However, exocytosis occurs several tens of seconds after the initation of the Ca2+ wave, which leads the authors to hypothesise that the influx of Ca2+ through transient receptor potential channel 1 (TRPC1) primes this membrane region for exocytic events.
