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