Contribution of septins to human platelet structure and function.
Contribution of septins to human platelet structure and function.
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DOI：
10.1016/j.isci.2022.104654
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发表时间：
2022-07-15
期刊：
影响因子：
5.8
通讯作者：
Weisel, John W.
中科院分区：
文献类型：
--
作者：
Kim, Oleg, V;Litvinov, Rustem, I;Mordakhanova, Elmira R.;Bi, Erfei;Vagin, Olga;Weisel, John W.
尽管在有核细胞中已经有了很好的研究，但它们在无核血小板中的作用仍然不清楚。在这里，我们阐明了Septins对人类血小板结构和功能的贡献。我们发现Septin-2和Septin-9主要分布在静息状态下的血小板周围，并与微管强烈共存。凝血酶激活血小板会导致间隔蛋白的聚集，并损害它们与微管的联系。用甲氯苯脲(FCF)抑制隔膜动力学可减少凝血酶诱导的隔膜致密化，并减少其与静息和活化血小板中微管的共存。暴露在FCF中会改变血小板的形状，这表明Septins稳定了血小板的细胞骨架。Fcf抑制血小板整合素αIIbβ3的激活，促进活化的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，提示Septin参与了这些过程。抑制Septin动力学实质上降低了血小板的收缩能力，并阻止了它们在纤维蛋白原涂层表面的扩散。总体而言，Septins对血小板的结构、激活和生物力学有很大的贡献。Septin-2和Septin-9与微管一起定位于血小板外周，血小板活化引起间隔蛋白的空间重排和聚集。Septin有助于血小板形态和活化标志物的表达。Septin组装支持血小板生物力学，包括伸展和收缩生物科学；细胞生物学；细胞生物学的功能方面；细胞生物学的综合方面
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. Septin-2 and Septin-9 localize at platelet periphery together with microtubules Platelet activation causes spatial rearrangement and clustering of septins Septins contribute to platelet morphology and expression of activation markers Septin assembly supports platelet biomechanics including spreading and contraction Biological sciences; Cell biology; Functional aspects of cell biology; Integrative aspects of cell biology
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影响因子：
16.6
作者：
Ageta-Ishihara, Natsumi;Miyata, Takaki;Ohshima, Chika;Watanabe, Masahiko;Sato, Yoshikatsu;Hamamura, Yuki;Higashiyama, Tetsuya;Mazitschek, Ralph;Bito, Haruhiko;Kinoshita, Makoto
通讯作者：
Kinoshita, Makoto
DOI：
10.1083/jcb.201305053
发表时间：
2013-11-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
El Amine N;Kechad A;Jananji S;Hickson GR
通讯作者：
Hickson GR
血块的收缩受损在前并预测术后静脉血栓栓塞。
影响因子：
4.6
作者：
Evtugina NG;Peshkova AD;Pichugin AA;Weisel JW;Litvinov RI
通讯作者：
Litvinov RI
影响因子：
5.5
作者：
Cavini IA;Leonardo DA;Rosa HVD;Castro DKSV;D'Muniz Pereira H;Valadares NF;Araujo APU;Garratt RC
通讯作者：
Garratt RC
影响因子：
3.7
作者：
Angelis, Dimitrios;Karasmanis, Eva Pauline;Spiliotis, Elias T.
通讯作者：
Spiliotis, Elias T.