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In this iBiology seminar, Dr. Avery August, professor and chair of Microbiology and Immunology, describes research into the molecular basis of mast cell degranulation. The binding of IgE to the Fc receptor on mast cells causes an increase in intracellular Ca2+ that is important for both cytokine production and degranulation. Experiments in August’s lab identified the actin binding protein Drebrin as the target of an immunosuppressant that can block mast cell degranulation. His lab generated Drebrin knockout mice and compared the response of mast cells from the knockout and wild type mice to Fc Receptor activation. They showed that the absence of Drebrin blocked Ca2+ influx upon receptor activation and blocked both degranulation and cytokine production. Further experiments investigated where Drebrin fits into the signaling pathways downstream of the Fc receptor.