Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions
Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions
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DOI：
10.1093/emboj/cdg588
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发表时间：
2003-11-17
期刊：
影响因子：
11.4
通讯作者：
Sidenius, N
中科院分区：
文献类型：
--
作者：
Cunningham, O;Andolfo, A;Sidenius, N
尿激酶型纤溶酶原激活剂受体（uPAR/CD87）是一种糖基磷脂酰肌醇锚定的膜蛋白，具有细胞外蛋白水解、细胞粘附、细胞迁移和增殖等多种功能。我们现在报道细胞表面 uPAR 二聚化，并且二聚体 uPAR 优先分配到耐去污剂的脂筏上。 uPAR的二聚化不需要筏分配，因为膜胆固醇的降低未能减少二聚化，并且作为跨膜uPAR嵌合体，其不分配至脂筏，也有效地二聚化。虽然 uPA 与 uPAR 的结合与其膜定位和二聚化状态无关，但 uPA 诱导的 uPAR 裂解在脂筏中强烈加速。与uPA相反，Vn的结合优先发生在筏相关二聚体uPAR上，并被胆固醇消耗完全阻断。
The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion.