The enigmatic nature of the triggering receptor expressed in myeloid cells -1 (TLT- 1).

The enigmatic nature of the triggering receptor expressed in myeloid cells -1 (TLT- 1).
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DOI:
10.1080/09537104.2021.1881948
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发表时间:
2021-08-18
期刊:
影响因子:
3.3
通讯作者:
--
中科院分区:
医学3区
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--
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受体是细胞上重要的药理靶点。髓样细胞(Trem)样转录本-1上表达的触发受体是一种丰富但鲜为人知的血小板受体。它是一种含有单一Ig结构域的受体,分离于静息血小板的α颗粒中,激活后带到血小板表面。在血小板上,整合素αIIbβ3是主要的受体,大约有80,000个拷贝。αIIbβ3是一种异二聚体多结构域结构,通过与血浆蛋白纤维蛋白原相互作用介导血小板聚集。抗血小板药物已经成功地针对αIIbβ3来控制血栓形成。与αIIbβ3一样,TLT-1也与纤维蛋白原结合,使其在血小板功能中的作用变得有些模糊。在这篇综述中,我们重点介绍了TLT-1的已知结构特征,并提出了理解TLT-1功能的挑战。在我们对活化后血小板表面动力学的分析中,我们提出了一个模型,在该模型中,TLT-1支持αIIbβ3作为一个机械感受器,可能引导血小板走向免疫功能。
Receptors are important pharmacological targets on cells. The Triggering Receptor Expressed on Myeloid Cells (TREM) – Like Transcript – 1 is an abundant, yet little understood, platelet receptor. It is a single Ig domain containing receptor isolated in the α-granules of resting platelets and brought to the platelet surface upon activation. On platelets, the integrin αIIbβ3 is the major receptor having roughly 80,000 copies. αIIbβ3 is a heterodimeric multidomain structure that mediates platelet aggregation through its interaction with the plasma protein fibrinogen. Anti-platelet drugs have successfully targeted αIIbβ3 to control thrombosis. Like αIIbβ3, TLT-1 also binds fibrinogen, making its role in platelet function somewhat obscure. In this review, we highlight the known structural features of TLT-1 and present the challenges of understanding TLT-1 function. In our analysis of the dynamics of the platelet surface after activation we propose a model in which TLT-1 supports αIIbβ3 function as a mechanoreceptor that may direct platelets toward immune function.
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