Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells
Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells
复制标题
受体动力学通过肥大细胞中肌动蛋白丝切蛋白的磷酸化调节肌动蛋白聚合状态
DOI：
10.1016/j.bbrc.2020.11.012
复制
发表时间：
2021
影响因子：
3.1
通讯作者：
Hirashima Naohide
中科院分区：
文献类型：
--
作者：
Suzuki Ruriko;Inoh Yoshikazu;Yokawa Satoru;Furuno Tadahide;Hirashima Naohide
通过多价抗原与高亲和力IgE受体（FcεRI）结合的IgE聚集诱导肥大细胞活化，而通过单体半抗原解聚聚集的FcεRI立即终止由Syk去磷酸化介导的脱粒，并介导细胞内Ca 2+浓度（[Ca 2 +]i）降低。肌动蛋白聚合状态与FcεRI聚集介导的肥大细胞活化密切相关。然而，肥大细胞中FcεRI的聚集-解聚与肌动蛋白重排之间的关系尚不清楚。多价抗原的加入迅速解聚肌动蛋白丝，而随后加入的单体半抗原迅速恢复肌动蛋白聚合。然而，肌动蛋白切割蛋白，在多价抗原刺激后几分钟暂时去磷酸化，并且单体半抗原的加入在30秒内迅速增加了cofilin磷酸化水平。去除细胞外Ca 2+而不是单体半抗原添加没有恢复cofilin磷酸化，表明单价半抗原引起的[Ca 2 +] i的显著降低不是肌动蛋白重排的关键原因。此外，单价半抗原并没有完全减少[Ca 2 +] i在肥大细胞预处理与jasplakinastatin，肌动蛋白解聚的抑制剂。这些结果表明，多价抗原诱导的肌动蛋白解聚介导的cofilin去磷酸化，和随后加入单价半抗原的F-肌动蛋白切断状态有效地引发肌动蛋白重新聚合的cofilin磷酸化。
Aggregation of IgE bound to the high-affinity IgE receptor (FcεRI) by a multivalent antigen induces mast cell activation, while disaggregation of aggregated FcεRI 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 FcεRI aggregation. However, the relation between aggregation-disaggregation of FcεRI 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+]iby monovalent hapten was not a critical reason for the actin rearrangement. Additionally, monovalent hapten did not completely reduce [Ca2+]iin 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.