Abstract Number: PB1648
Meeting: ISTH 2020 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: Platelets are blood cells that play an important role in hemostasis and thrombosis. Activated platelets change shape due to reorganization of cytoskeleton. Septins, a family of GTP-binding cytoskeletal proteins, are implicated in cytokinesis and mitosis of nucleated cells, but their role in platelets is largely unknown.
Aims: To study the septins in resting and activated platelets and their contribution to platelet morphology and functions.
Methods: Confocal microscopy, flow cytometry, biomechanical and biochemical assays were used to examine structural and functional changes in human platelets. Septins 2 and 9 were immunostained in resting and activated platelets, either spread on a fibrinogen-coated surface or contracting within a 3D plasma clot. Clot contraction was assessed by tracking the clot size.
Results: In resting platelets, septin 2 concentrated at the cell periphery, colocalizing with the microtubule marginal ring, while septin 9 was distributed as small patches over the cell volume, often with a peripheral localization. In thrombin-activated platelets, septins were also observed in filopodia. Activation with thrombin resulted in a 2-fold increase of septin intensity. Inhibition of septin dynamics with forchlorfenuron (FCF) caused dose-dependent perturbations, including a substantial decrease of platelet roundness and surface curvature. In FCF-pretreated platelets activated with TRAP, expression of activated integrin αIIbβ3 was significantly suppressed. FCF impeded clot contraction with a 6-fold increase of the lag-time and up to a 3-fold decrease of the extent of contraction. Alterations in septin structure caused by FCF abrogated platelet spreading by 50% and accelerated thrombin-induced platelet fragmentation.
Conclusions: Septins are important for stabilizing platelet shape and supporting platelet integrity; septins are involved in platelet biomechanical functions, such as contractility and adhesion.
Funding: Work supported by the Program of Competitive Growth at KFU and grants 18-415-160004, 19-015-00075, 20-015-00257 from the Russian Foundation for Basic Research, and 17SDG33680177 from AHA.
To cite this abstract in AMA style:
Kim O, Mordakhanova E, Vagin O, Litvinov R, Weisel J. Septins Contribute to Platelet Shape and Functionality [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/septins-contribute-to-platelet-shape-and-functionality/. Accessed January 26, 2021.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/septins-contribute-to-platelet-shape-and-functionality/