Abstract Number: PB0968
Meeting: ISTH 2021 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: Platelets are blood cells playing an important role in hemostasis and thrombosis. Activated platelets change shape due to cytoskeleton remodeling. Septins, a family of GTP-binding cytoskeletal proteins, are implicated in cytokinesis, membrane remodeling and intracellular trafficking of nucleated cells, but their contribution to platelet biology is largely unknown.
Aims: To examine septins in resting and activated human platelets and their role in platelet structure 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, and microtubules were stained in resting and activated platelets as well as in platelets spread on a fibrinogen-coated surface.
Results: In resting platelets, septin 2 concentrated at the cell periphery, while septin 9 was distributed as small patches over the cell volume, often with a peripheral localization. Both septins colocalized with a microtubule marginal band. In thrombin-activated platelets, septins formed intense fluorescent clusters. Activation with thrombin resulted in a 2-fold increase of septin intensity and decrease in colocalization between septins and α-tubulin. Inhibition of septin assembly with forchlorfenuron (FCF) resulted in disruption and thickening of septin 2 ring, elongation of septin structures, reduction of colocalization between septins and α-tubulin, a 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. Inhibition of septin assembly 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 surface markers expression and biomechanical functions, such as contractility and adhesion.
Funding: Work supported by AHA grant 17SDG33680177.
To cite this abstract in AMA style:
Kim OV, Vagin O, Litvinov RI, Weisel JW. The Role of Septins in Platelet Structure and Function [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-role-of-septins-in-platelet-structure-and-function/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-role-of-septins-in-platelet-structure-and-function/