Cutting edge: Drebrin-regulated actin dynamics regulate ige-dependent mast cell activation and allergic responses

Mast cells play critical roles in allergic responses. Calcium signaling controls the function of these cells, and a role for actin in regulating calcium influx into cells has been suggested. We have previously identified the actin reorganizing protein Drebrin as a target of the immunosuppressant 3,5-bistrifluoromethyl pyrazole, which inhibits calcium influx into cells. In this study, we show that Drebrin^-/-2 mice exhibit reduced IgE-mediated histamine release and passive systemic anaphylaxis, and Drebrin^-/-2 mast cells also exhibit defects in FceRI-mediated degranulation. Drebrin^-/-2 mast cells exhibit defects in actin cytoskeleton organization and calcium responses downstream of the FceRI, and agents that relieve actin reorganization rescue mast cell FceRI-induced degranulation. Our results indicate that Drebrin regulates the actin cytoskeleton and calcium responses in mast cells, thus regulating mast cell function in vivo.