LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation

Cell. 1992 Oct 30;71(3):411-21. doi: 10.1016/0092-8674(92)90511-a.


The low density lipoprotein receptor-related protein (LRP) is a large multifunctional clearance receptor that has been implicated in the hepatic uptake of chylomicron remnants and in the removal of protease-inhibitor complexes from the circulation and from the extracellular space. Disruption of the LRP gene in mice blocks development of LRP-/- embryos around the implantation stage. The expression pattern of LRP in the postimplantation stage embryo is identical to that of urokinase, a plasminogen activator that confers invasive properties to migrating cells. We demonstrate that LRP mediates uptake and degradation of urokinase-type plasminogen activator-plasminogen activator inhibitor 1 complexes and propose that the inability of the giant cells to remove the inactive protease complexes from their surfaces interferes with implantation of the embryo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Mutational Analysis
  • Embryo Implantation / physiology*
  • Endocytosis
  • Female
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Stem Cells
  • Trophoblasts / metabolism*
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Proteins
  • Plasminogen Activator Inhibitor 1
  • Receptors, Immunologic
  • Urokinase-Type Plasminogen Activator