title: Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions.
abstract: 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.
authors: Molecular Genetics Unit, Department of Molecular Biology and Functional Genomics, Università Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milan, Italy.
authors: Orla
authors: O
authors: Cunningham
authors: Annapaola
authors: A
authors: Andolfo
authors: Maria Lisa
authors: ML
authors: Santovito
authors: Lucia
authors: L
authors: Iuzzolino
authors: Francesco
authors: F
authors: Blasi
authors: Nicolai
authors: N
authors: Sidenius
mesh_terms: D019281:Dimerization; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator
chemical_list: D016326:Extracellular Matrix Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator