Actin polymerization regulates glycoprotein Ibα shedding

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

Competing interests

The authors declare no conflict of interest.

Author contributions

KZ and RY designed the research, collected and analyzed data. KZ wrote the paper. KZ, YX, MY performed experiments. WX, LZ, RH and Khan. M. S helped to analyzed data. KD initiated and supervised the project, designed research, analyzed and interpreted results, wrote the paper. All authors reviewed the manuscript.

Additional information

Funding

This work was funded by Key Program of International Cooperation and Exchange of the National Natural Science Foundation of China (NO. 81820108003)); National Natural Science Foundation of China(NO. 81570102, 81770117 and 82070121).