Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Yue Xia
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Mengnan Yang
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Weiling Xiao
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Lili Zhao
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Renping Hu
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Khan Muhammad Shoaib
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Rong Yan
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Kesheng Dai
Jiangsu Institute of Hematology, the First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health
Glycoprotein (GP) Ibα shedding mediated by ADAM17 (a disintegrin and metalloproteinase 17) plays an important role in negatively regulating platelet function and thrombus formation. However, the mechanism of GPIbα shedding remains elusive. Here, we show that jasplakinolide (an actin-polymerizing peptide)-induced actin polymerization results in GPIbα shedding and impairs platelet function. Thrombin and A23187-induced GPIbα shedding is increased by jasplakinolide; in contrast, GPIbα shedding is reduced by a depolymerization regent (cytochalasin B). We find that actin polymerization activates calpain leading to filamin A hydrolyzation. We further demonstrate that the interaction of filamin A with the cytoplasmic domain of GPIbα plays a critical role in regulating actin polymerization-induced GPIbα shedding. Taken together, these data demonstrate that actin polymerization regulates ADAM17-mediated GPIbα shedding, suggesting a novel strategy to negatively regulate platelet function.
