1. Academic Validation
  2. Actin polymerization regulates glycoprotein Ibα shedding

Actin polymerization regulates glycoprotein Ibα shedding

  • Platelets. 2022 Apr 3;33(3):381-389. doi: 10.1080/09537104.2021.1922882.
Kangxi Zhou 1 Yue Xia 1 Mengnan Yang 1 Weiling Xiao 1 Lili Zhao 1 Renping Hu 1 Khan Muhammad Shoaib 1 Rong Yan 1 Kesheng Dai 1
Affiliations

Affiliation

  • 1 Medical College, 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, Suzhou, Jiangsu, China.
Abstract

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.

Keywords

Actin polymerization; calpain; filamin a; gpibα shedding; platelet.

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