Microfilaments make mast cells migrate (rather than degranulate).

Expression of the high-affinity receptor for IgE (FcεRI) provides mast cells with the ability to react in a proinflammatory manner to antigens (Ags). In particular, the immediate secretion of preformed mediators from secretory lysosomes (degranulation) is typical for FcεRI-mediated mast cell activation. In addition to the FcεRI, the stem cell factor receptor, KIT, is expressed at high levels on the surface of mast cells. KIT activation controls mast cell differentiation and survival in vivo and potently stimulates the chemotaxis of these cells. Although FcεRI and KIT initiate many of the same early signaling events in mast cells, FcεRI activation results in potent degranulation and a poor chemotactic response while KIT activation triggers very little degranulation and a strong chemotactic response. Novel data published in this issue of the European Journal of Immunology [Smrž et al. Eur. J. Immunol. 2013. 43: 1873-1882] demonstrate that actin de- and repolymerization, involved in both degranulation and chemotaxis, make all the difference: Pharmacological suppression of F-actin formation converts activated KIT into a strong degranulator. The possible implications for mast cell physiology and pathophysiology are discussed in this Commentary.