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Regulation of platelet membrane protein shedding in health and disease

机译:血小板膜蛋白在健康与疾病中的调节

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摘要

Extracellular proteolysis of platelet plasma membrane proteins is an event that ensues platelet activation. Shedding of surface receptors such as glycoprotein (GP) Iba, GPV and GPVI as well as externalized proteins P-selectin and CD40L releases soluble ectodomain fragments that are subsequently detectable in plasma. This results in the irreversible functional downregulation of platelet receptor-mediated adhesive interactions and the generation of biologically active fragments. In this review, we describe molecular insights into the regulation of platelet receptor and ligand shedding in health and disease. The scope of this review is specially focused on GPIb alpha, GPV, GPVI, P-selectin and CD40L where we: (1) describe the basic physiological regulation of expression and shedding of these proteins in hemostasis illustrate alterations in receptor expression during (2) apoptosis and (3) ex vivo storage relevant for blood banking purposes; (4) discuss considerations to be made when analyzing and interpreting shedding of platelet membrane proteins and finally; (5) collate clinical evidence that quantify these platelet proteins during disease.
机译:血小板质膜蛋白的细胞外蛋白水解是导致血小板活化的一个事件。表面受体如糖蛋白(GP)Iba、GPV和GPVI以及外化蛋白P-选择素和CD40L的脱落会释放可溶性外域片段,这些片段随后可在血浆中检测到。这导致血小板受体介导的粘附相互作用的不可逆功能下调,并产生生物活性片段。在这篇综述中,我们描述了在健康和疾病中血小板受体和配体脱落调节的分子见解。本综述的范围特别关注GPIbα、GPV、GPVI、P-选择素和CD40L,其中我们:(1)描述了这些蛋白质在止血过程中表达和脱落的基本生理调节,说明了(2)凋亡过程中受体表达的变化,以及(3)与血库相关的体外储存;(4) 讨论分析和解释血小板膜蛋白脱落时应考虑的事项,最后;(5) 整理疾病期间量化这些血小板蛋白的临床证据。

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