Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization

Olga Y. Barmina, Hobart W. Walling, Gerald J. Fiacco, José M.P. Freije, Carlos López-Otín, John J. Jeffrey, Nicola C. Partridge

Research output: Contribution to journalArticle

Abstract

We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptor-related protein. Ligand blot analysis shows that 125I-collagenase-3 binds specifically to two proteins (~170 kDa and ~600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wild-type mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor- related protein mediating internalization.

Original languageEnglish (US)
Pages (from-to)30087-30093
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number42
DOIs
StatePublished - Oct 15 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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