Evidence for the selective association of a subpopulation of GPIIb-IIIa with the actin cytoskeletons of thrombin-activated platelets.
Evidence for the selective association of a subpopulation of GPIIb-IIIa with the actin cytoskeletons of thrombin-activated platelets.
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DOI：
10.1083/jcb.121.6.1329
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发表时间：
1993-06
影响因子：
7.8
通讯作者：
Beckerle, M C
中科院分区：
文献类型：
--
作者：
Bertagnolli, M E;Beckerle, M C
血小板的激活会触发一系列的反应，导致血栓的形成和回缩。在这些反应中，细胞外基质成分和血小板肌动蛋白细胞骨架之间建立了整合素介导的跨膜连接。在这里，我们报道了主要的血小板整合素的一个特定亚群，糖蛋白IIb-IIIa(GPIIb-IIIa)(也被称为αIIbβ3整合素)，在血小板激活反应中被整合到不溶于洗涤剂的血小板肌动蛋白细胞骨架中。GPIIb-IIIa的细胞骨架结合不依赖于血小板聚集和纤维蛋白沉积，并且对细胞松弛素D治疗敏感。Western免疫印迹分析表明，当凝血酶激活时，大约22%的细胞总GPIIb-IIIa与肌动蛋白细胞骨架结合，这种方式与塔林、α-肌动蛋白或纽蛋白在复合体中的检测无关。我们发现，细胞骨架相关的GPIIb-IIIa来自细胞内，因为在血小板激活之前，它不能用于乳酸过氧化物酶催化的放射性碘化。静息的血小板中存在两个GPIIb-IIIa的细胞内来源：与α颗粒分泌室相关的GPIIb-IIIa以及表面连接的小管系统的表面不可触及的区域。有趣的是，在凝血酶激活的血小板中发生的α颗粒分泌，导致细胞内的GPIIb-IIIa移位到质膜，似乎是我们观察到的GPIIb-IIIa的细胞骨架掺入所必需的。总之，我们的数据提供了证据，证明在没有血小板聚集的情况下，当凝血酶激活时，来自细胞内来源的GPIIb-IIIa亚群选择性地与血小板的肌动蛋白细胞骨架相连。
Activation of blood platelets triggers a series of responses leading to the formation and retraction of blood clots. Among these responses is the establishment of integrin-mediated transmembrane connections between extracellular matrix components and the actin cytoskeleton of the platelet. Here we report that a specific subpopulation of the major platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa) (also referred to as alpha IIb beta 3 integrin), becomes incorporated into the detergent- insoluble actin cytoskeleton of platelets during the platelet activation response. The cytoskeletal association of GPIIb-IIIa is independent of platelet aggregation and fibrin sedimentation and is sensitive to cytochalasin D treatment. As determined by Western immunoblot analysis, approximately 22% of the total cellular GPIIb-IIIa becomes associated with the actin cytoskeleton upon thrombin activation in a manner that is independent of the detection of talin, alpha- actinin, or vinculin in the complex. We found that the cytoskeleton- associated GPIIb-IIIa is derived from an intracellular source since it is not available for lactoperoxidase-catalyzed radioiodination before platelet activation. Two intracellular sources of GPIIb-IIIa are present in resting platelets: GPIIb-IIIa associated with the alpha- granule secretory compartment as well as surface-inaccessible domains of the surface-connected canalicular system. Interestingly, alpha- granule secretion, which occurs in thrombin-activated platelets and results in the translocation of intracellular GPIIb-IIIa to the plasma membrane, appears to be required for the cytoskeleton incorporation of GPIIb-IIIa that we observe. Collectively, our data provide evidence that a subpopulation of GPIIb-IIIa derived from an intracellular source is selectively linked to the actin cytoskeleton of platelets upon thrombin activation in the absence of platelet aggregation.