Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen
Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen
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DOI：
10.1182/blood-2003-02-0591
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发表时间：
2003-08-15
期刊：
影响因子：
20.3
通讯作者：
Naik, MU
中科院分区：
文献类型：
--
作者：
Naik, UP;Naik, MU
血小板在固定纤维蛋白原（Fg）上的扩散涉及多个形态阶段的进展，尽管这些阶段各不相同，但其机制尚未得到很好的理解。在这里，我们证明GPIIb/IIIa与钙和整合素结合蛋白（CIB）之间的关联是血小板扩散过程所必需的。当血小板粘附在固定的Fg上时，CIB定位于瞬时形成的丝状伪足，然后沿着扩散的血小板的膜周重新弥散分布。免疫沉淀分析表明，CIB和糖蛋白IIb/IIIa （GPIIb/IIIa）在血小板粘附于固定化Fg时相互作用，并共同与血小板细胞骨架结合。将抗cib抗体或GPIIb细胞质肽引入血小板可阻断板足而非丝状足的形成。GPIIb肽诱导的血小板扩散抑制通过重组CIB蛋白的掺入得以恢复，这表明CIB和GPIIb/IIIa之间的相互作用是从丝状形态发展到扩散形态的必要条件。此外，抗cib -或GPIIb肽诱导的血小板扩散抑制可以通过添加外源性二磷酸腺苷（ADP）来克服。这些数据表明，CIB-GPIIb/IIIa复合体的形成可能是下游信号事件启动的必要条件，如ADP分泌，导致血小板扩散。(C) 2003年由美国血液病学会出版。
Platelet spreading on immobilized fibrinogen (Fg) involves progression through a number of morphologic stages that, although distinctive, are not well understood mechanistically. Here we demonstrate that an association between GPIIb/IIIa and calcium- and integrin-binding protein (CIB) is required for the process of platelet spreading. Upon platelet adhesion to immobilized Fg, CIB localizes to the transiently formed filopodia and then redistributes diffusely along the membrane periphery of spread platelets. Immunoprecipitation analyses indicate that CIB and glycoprotein IIb/IIIa (GPIIb/IIIa) interact with each other as platelets adhere to immobilized Fg, and together they associate with the platelet cytoskeleton. Introduction of anti-CIB antibody or GPIIb cytoplasmic peptide into platelets blocks lamellipodia but not filopodia formation. GPIIb peptide-induced inhibition of platelet spreading is recovered by the incorporation of recombinant CIB protein, suggesting that interaction between CIB and GPIIb/IIIa is required for progression from filopodial to spread morphologies. Further, anti-CIB- or GPIIb peptide-induced inhibition of platelet spreading can be overcome by the addition of exogenous adenosine diphosphate (ADP). These data suggest that formation of the CIB-GPIIb/IIIa complex may be necessary for initiation of downstream signaling events, such as ADP secretion, that lead to platelet spreading. (C) 2003 by The American Society of Hematology.