Adhesive surface determines raft composition in platelets adhered under flow
Adhesive surface determines raft composition in platelets adhered under flow
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DOI：
10.1111/j.1538-7836.2005.01597.x
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发表时间：
2005-11
影响因子：
10.4
通讯作者：
M. Lier;F. Lee;R. Farndale;G. Gorter;S. Verhoef;Yoshiko Ohno-Iwashita;Jan-Willem N. Akkerman;H. F. Heijnen
中科院分区：
文献类型：
--
作者：
M. Lier;F. Lee;R. Farndale;G. Gorter;S. Verhoef;Yoshiko Ohno-Iwashita;Jan-Willem N. Akkerman;H. F. Heijnen
摘要粘附于血管性血友病因子（VWF）诱导血小板扩散，而粘附于胶原诱导聚集。在这里，我们报告了富含胆固醇的结构域（CRD）或筏在控制这些反应的受体聚集中起着关键作用。粘附于VWF和胶原的血小板显示CRD集中在丝状伪足中，其含有VWF受体糖蛋白（GP）Ibα和胶原受体GPVI。CRD的生化分析显示，VWF粘附的血小板中GPIbα（但不是GPVI）富集了三倍，胶原蛋白粘附的血小板中GPVI（但不是GPIbα）富集了四倍。胆固醇的消耗（i）保持初始粘附不变，（ii）抑制VWF上的铺展和胶原上的聚集体形成，（iii）保持丝状伪足形成完整，（iv）减少GPIbα而不是GPVI在丝状伪足中的定位。这些数据表明，粘附基质决定了CRD的组成，胆固醇对GPIbα的再分布至关重要，但对GPVI无关。
Summary. Adhesion to von Willebrand factor (VWF) induces platelet spreading, whereas adhesion to collagen induces aggregation. Here we report that cholesterol‐rich domains (CRDs) or rafts play a critical role in clustering of receptors that control these responses. Platelets adhered to VWF and collagen show CRDs concentrated in filopodia which contain both the VWF receptor glycoprotein (GP) Ibα and the collagen receptor GPVI. Biochemical analysis of CRDs shows a threefold enrichment of GPIbα (but not GPVI) in VWF‐adhered platelets and a fourfold enrichment of GPVI (but not GPIbα) in collagen‐adhered platelets. Depletion of cholesterol (i) leaves the initial adhesion unchanged, (ii) inhibits spreading on VWF and aggregate formation on collagen, (iii) leaves filopodia formation intact, and (iv) reduces the localization in filopodia of GPIbα but not of GPVI. These data show that the adhesive substrate determines the composition of CRDs, and that cholesterol is crucial for redistribution of GPIbα but not of GPVI.