Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells

Aggregation of IgE bound to the high-affinity IgE receptor (Fc epsilon RI) by a multivalent antigen induces mast cell activation, while disaggregation of aggregated Fc epsilon RI by monomer hapten immediately terminates degranulation mediated by dephosphorylation of Syk and mediates a decrease in intracellular Ca2+ concentration ([Ca2+](i)). The actin polymerization state is intimately involved in mast cell activation mediated by Fc epsilon RI aggregation. However, the relation between aggregation-disaggregation of Fc epsilon RI and actin rearrangement in mast cells is not well understood. The addition of a multivalent antigen rapidly depolymerized actin filaments, while the subsequent addition of monomer hapten rapidly recovered actin polymerization. Whereas cofilin, an actin-severing protein, was temporally dephosphorylated several minutes after a multivalent antigen stimulation and the addition of monomer hapten rapidly increased cofilin phosphorylation level within 30 s. The removal of extracellular Ca2+ instead of monomer hapten addition did not restore cofilin phosphorylation, suggesting that the significant decrease in [Ca2+](i) by monovalent hapten was not a critical reason for the actin rearrangement. Additionally, monovalent hapten did not completely reduce [Ca2+](i) in mast cells pretreated with jasplakinolide, an inhibitor of actin depolymerization. These results suggest that the multivalent antigen-induced actin depolymerization mediated by cofilin dephosphorylation, and the subsequent addition of monovalent hapten in the F-actin severing state efficiently elicited actin re-polymerization by cofilin phosphorylation. (C) 2020 Elsevier Inc. All rights reserved.