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  • The EMBO Journal (2003) 22, 5994 - 6003
  • doi:10.1093/emboj/cdg588

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

Orla Cunningham1, Annapaola Andolfo1, Maria Lisa Santovito1, Lucia Iuzzolino2, Francesco Blasi1 and Nicolai Sidenius1

  1. Molecular Genetics Unit, Department of Molecular Biology and Functional Genomics, FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
  2. Biocrystallography Unit, DIBIT, Università Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milan, and IFOM, FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy

Correspondence to:

Nicolai Sidenius, E-mail: sidenius.nicolai@hsr.it

Received 12 June 2003; Accepted 2 October 2003; Revised 23 September 2003

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.

  • Keywords:

    • dimerization,
    • GPI,
    • lipid rafts,
    • uPAR,
    • Vn