Recycling of the urokinase receptor upon internalization of the uPA: serpin complexes

Anders Nykjaer, Massimo Conese, Erik I. Christensen, David Olson, Ottavio Cremona, Jørgen Gliemann, Francesco Blasi

Research output: Contribution to journalArticlepeer-review

Abstract

The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not internalize free urokinase (uPA) but readily internalizes and degrades uPA:serpin complexes in a process that requires the α2-macroglobulin receptor/low density lipoprotein receptor-related protein (α2MR-LRP). This process is accompanied by the internalization of uPAR which renders it resistant to phosphatidylinositol-specific phospholipase C (PI-PLC). In this paper we show that during internalization of uPA:serpins at 37°C, analysed by FACScan, immunofluorescence and immunoelectron microscopy, an initial decrease of cell surface uPAR was observed, followed by its reappearance at later times. This effect was not due to redistribution of previously intracellular receptors, nor to the surface expression of newly synthesized uPAR. Recycling was directly demonstrated in cell surface-biotinylated, uPA:PAI-1-exposed cells in which biotinylated uPAR was first internalized and subsequently recycled back to the surface upon incubation at 37°C. In fact, uPAR was resistant to PI-PLC after the 4°C binding of uPA:PAI-1 to biotinylated cells, but upon incubation at 37°C PI-PLC-sensitive biotinylated uPAR reappeared at the cell surface. Binding of uPA:PAI-1 by uPAR, while essential to initiate the whole process, was, however, dispensable at later stages as both internalization and recycling of uPAR could be observed also after dissociation of the bound ligand from the cell surface.

Original languageEnglish
Pages (from-to)2610-2620
Number of pages11
JournalEMBO Journal
Volume16
Issue number10
DOIs
Publication statusPublished - May 15 1997

Keywords

  • Internalization
  • Recycling
  • uPA:serpin complex
  • Urokinase receptor

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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