1. Gelsolin regulates receptor-mediated and fluid-phase endocytosis in platelets.
- Author
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Paul M, Hong F, Falet H, and Kim H
- Subjects
- Animals, Mice, Actin Cytoskeleton metabolism, Actins metabolism, Adenosine Diphosphate metabolism, Cytochalasin D pharmacology, Depsipeptides, Fibrinogen metabolism, Mice, Inbred C57BL, Mice, Knockout, Blood Platelets cytology, Blood Platelets metabolism, Endocytosis, Gelsolin metabolism
- Abstract
Background: Endocytosis is the process by which platelets incorporate extracellular molecules into their secretory granules. Endocytosis is mediated by the actin cytoskeleton in nucleated cells; however, the endocytic mechanisms in platelets are undefined., Objectives: To better understand platelet endocytosis, we studied gelsolin (Gsn), an actin-severing protein that promotes actin assembly., Methods: Mouse platelets from Gsn-null (Gsn
-/- ) and wild-type (WT) controls were used. The uptake of fluorescent cargo molecules was compared as a measure of their endocytic efficiency. Receptor-mediated endocytosis was measured by the uptake of fibrinogen and transferrin; fluid-phase endocytosis was monitored by the uptake of fluorescent dextrans., Results: Adenosine diphosphate (ADP)-stimulated WT platelets readily internalized both receptor-mediated and fluid-phase cargoes. In contrast, Gsn-/- platelets showed a severe defect in the endocytosis of both types of cargo. The treatment of WT platelets with the actin-disrupting drugs cytochalasin D and jasplakinolide also reduced endocytosis. Notably, the individual and combined effects of Gsn deletion and drug treatment were similar for both receptor-mediated and fluid-phase endocytosis, indicating that Gsn mediates endocytosis via its action on the actin cytoskeleton., Conclusion: Our study demonstrates that Gsn plays a key role in the uptake of bioactive mediators by platelets., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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