uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion

Lars H. Engelholm, Karin List, Sarah Netzel-Arnett, Edna Cukierman, David J. Mitola, Hannah Aaronson, Lars Kjøller, Jørgen K. Larsen, Kenneth M. Yamada, Dudley K. Strickland, Kenn Holmbeck, Keld Danø, Henning Birkedal-Hansen, Niels Behrendt, Thomas H. Bugge

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

The uptake and lysosomal degradation of collagen by fibroblasts constitute a major pathway in the turn-over of connective tissue. However, the molecular mechanisms governing this pathway are poorly understood. Here, we show that the urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180, a novel mesenchymally expressed member of the macrophage mannose receptor family of endocytic receptors, is a key player in this process. Fibroblasts from mice with a targeted deletion in the uPARAP/Endo180 gene displayed a near to complete abrogation of collagen endocytosis. Furthermore, these cells had diminished initial adhesion to a range of different collagens, as well as impaired migration on fibrillar collagen. These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions.

Original languageEnglish
Pages (from-to)1009-1015
Number of pages7
JournalJournal of Cell Biology
Volume160
Issue number7
DOIs
StatePublished - Apr 3 2003

Keywords

  • Cell adhesion
  • Integrin
  • Matrix internalization
  • Matrix metalloproteinase
  • uPAR

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