LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation.
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.
Herz
J
J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Clouthier
D E
DE
Hammer
R E
RE
D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D010064:Embryo Implantation / Q000502:physiology*; D004705:Endocytosis; D005260:Female; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells; D014327:Trophoblasts / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008565:Membrane Proteins; D017395:Plasminogen Activator Inhibitor 1; D011971:Receptors, Immunologic; D014568:Urokinase-Type Plasminogen Activator