Kim Oleg V, Litvinov Rustem I, Mordakhanova Elmira R, Bi Erfei, Vagin Olga, Weisel John W
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
iScience. 2022 Jun 22;25(7):104654. doi: 10.1016/j.isci.2022.104654. eCollection 2022 Jul 15.
Although septins have been well-studied in nucleated cells, their role in anucleate blood platelets remains obscure. Here, we elucidate the contribution of septins to human platelet structure and functionality. We show that Septin-2 and Septin-9 are predominantly distributed at the periphery of resting platelets and co-localize strongly with microtubules. Activation of platelets by thrombin causes clustering of septins and impairs their association with microtubules. Inhibition of septin dynamics with forchlorfenuron (FCF) reduces thrombin-induced densification of septins and lessens their colocalization with microtubules in resting and activated platelets. Exposure to FCF alters platelet shape, suggesting that septins stabilize platelet cytoskeleton. FCF suppresses platelet integrin αIIbβ3 activation, promotes phosphatidylserine exposure on activated platelets, and induces P-selectin expression on resting platelets, suggesting septin involvement in these processes. Inhibition of septin dynamics substantially reduces platelet contractility and abrogates their spreading on fibrinogen-coated surfaces. Overall, septins strongly contribute to platelet structure, activation and biomechanics.
尽管septin蛋白在有核细胞中已得到充分研究，但其在无核血小板中的作用仍不清楚。在此，我们阐明了septin蛋白对人血小板结构和功能的作用。我们发现，Septin-2和Septin-9主要分布在静息血小板的外周，并与微管强烈共定位。凝血酶激活血小板会导致septin蛋白聚集，并削弱它们与微管的结合。用氯吡脲（FCF）抑制septin蛋白的动态变化可减少凝血酶诱导的septin蛋白致密化，并减少其在静息和激活血小板中与微管的共定位。暴露于FCF会改变血小板形状，表明septin蛋白可稳定血小板细胞骨架。FCF抑制血小板整合素αIIbβ3激活，促进激活血小板上磷脂酰丝氨酸的暴露，并诱导静息血小板上P-选择素的表达，表明septin蛋白参与了这些过程。抑制septin蛋白的动态变化会显著降低血小板的收缩性，并消除它们在纤维蛋白原包被表面的铺展。总体而言，septin蛋白对血小板结构、激活和生物力学有重要作用。
