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

Joachim Herz; David E. Clouthier; Robert E Hammer

doi:10.1016/0092-8674(92)90511-A

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

Joachim Herz, David E. Clouthier, Robert E Hammer

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Abstract

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.

Original language	English (US)
Pages (from-to)	411-421
Number of pages	11
Journal	Cell
Volume	71
Issue number	3
DOIs	https://doi.org/10.1016/0092-8674(92)90511-A
State	Published - Oct 30 1992

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/0092-8674(92)90511-A

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

abstract = "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.",

author = "Joachim Herz and Clouthier, {David E.} and Hammer, {Robert E}",

note = "Funding Information: We are indebted to Allan Bradley for sharing the A&l stem cell line and the ST0 feeder cell line; to Phil Soriano for vectors and numerous helpful discussions; to Jack Henkin (Abbott Laboratories), Kim Orth, and Ed Madison for providing UPA, AT fragment, and PAI-1: and to Wen-Ling Niu and Sharon Tucker for excellent technical assistance. We further thank Mike Brown and Joe Goldstein for encouragement, helpful suggestions, and critical reading of this manuscript. The work reported in this paper was supported by grants from the National Institutes of Health (HL 20948), the Howard Hughes Medical Institute, the Lucille P. Markey Charitable Trust, and the Perot Family Foundation. J. H. was supported by the Syntex Scholar Program and is a Lucille P. Markey Scholar.",

year = "1992",

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doi = "10.1016/0092-8674(92)90511-A",

language = "English (US)",

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pages = "411--421",

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T1 - LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation

AU - Herz, Joachim

AU - Clouthier, David E.

AU - Hammer, Robert E

N1 - Funding Information: We are indebted to Allan Bradley for sharing the A&l stem cell line and the ST0 feeder cell line; to Phil Soriano for vectors and numerous helpful discussions; to Jack Henkin (Abbott Laboratories), Kim Orth, and Ed Madison for providing UPA, AT fragment, and PAI-1: and to Wen-Ling Niu and Sharon Tucker for excellent technical assistance. We further thank Mike Brown and Joe Goldstein for encouragement, helpful suggestions, and critical reading of this manuscript. The work reported in this paper was supported by grants from the National Institutes of Health (HL 20948), the Howard Hughes Medical Institute, the Lucille P. Markey Charitable Trust, and the Perot Family Foundation. J. H. was supported by the Syntex Scholar Program and is a Lucille P. Markey Scholar.

PY - 1992/10/30

Y1 - 1992/10/30

N2 - 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.

AB - 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.

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

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