Multiple protein disulfide isomerases support thrombosis.
Multiple protein disulfide isomerases support thrombosis.
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DOI：
10.1097/moh.0000000000000449
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发表时间：
2018-09
影响因子：
3.2
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Essex DW;Wu Y
本文综述了血栓形成所需的蛋白质二硫键异构酶（PDI）家族的新成员的最新研究结果。二十年前，PDI被证明介导血小板聚集，十年前，PDI被证明支持体内血栓形成。随后，该内质网酶家族的其他成员ERp57和ERp5被证明支持血栓形成。第四个成员，ERp72，最近被证明是所需的血小板积累和纤维蛋白沉积在体内。这些酶都不能单独支持这些过程。此外，缺乏特定PDI的血小板的聚集仅由缺失的PDI恢复。这意味着每个PDI在αIIbβ3纤维蛋白原受体和血小板聚集的活化中具有不同的作用。在αIIbβ3的两个亚基中均可标记游离巯基，表明基于半胱氨酸的反应参与将构象变化从该整联蛋白的胞质尾部传递至整联蛋白头部。PDI家族的多个成员支持血小板功能，以及在这些过程中具有不同作用的止血和血栓形成。每种酶的单个半胱氨酸靶点以及这些酶如何整合到支持止血和血栓形成的网络中仍有待阐明。
This review provides an overview of recent findings on new members of the protein disulfide isomerase (PDI) family required for thrombosis. Twenty years ago PDI was shown to mediate platelet aggregation, and ten years ago PDI was shown to support thrombosis in vivo. Subsequently, other members of this endoplasmic reticulum family of enzymes, ERp57 and ERp5, were demonstrated to support thrombosis. A fourth member, ERp72, was recently shown to be required for platelet accumulation and fibrin deposition in vivo. None of these enzymes can individually support these processes. Moreover, aggregation of platelets deficient in a specific PDI is only recovered by the PDI that is missing. This implies that each PDI has a distinct role in activation of the αIIbβ3 fibrinogen receptor and platelet aggregation. Free thiols can be labeled in both subunits of αIIbβ3 suggesting cysteine-based reactions are involved in relaying conformational changes from the cytoplasmic tails to the integrin headpiece of this integrin. Multiple members of the PDI family support platelet function, and hemostasis and thrombosis with distinct roles in these processes. The individual cysteine targets of each enzyme and how these enzymes are integrated into a network that supports hemostasis and thrombosis remain to be elucidated.