Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment

EMBO J. 1990 Jun;9(6):1769-76.

Abstract

The low density lipoprotein receptor-related protein (LRP) is a cell surface glycoprotein that binds and transports plasma lipoproteins enriched in apolipoprotein E. It is synthesized in the endoplasmic reticulum as a transmembrane glycosylated precursor that migrates with an apparent molecular mass of about 600 kd on SDS-polyacrylamide gels. After it reaches the Golgi complex, the protein is cleaved to generate two subunits with apparent molecular masses of approximately 515 and 85 kd respectively. The larger NH2-terminal alpha-subunit lacks a membrane-spanning region. It remains attached to the membrane through noncovalent association with the smaller COOH-terminal beta-subunit. Proteolysis occurs at the sequence RHRR, which resembles the sequence RKRR at the proteolytic site in the receptors for insulin and insulin-like growth factor-1 (IGF-1), the only other cell surface receptors known to undergo proteolytic processing. Proteolysis of LRP occurs coincident with the conversion of the N-linked carbohydrates to the mature endoglycosidase H-resistant, neuraminidase-sensitive form. Proteolysis is prevented by brefeldin A, which blocks transport to the Golgi complex. These data raise the possibility that LRP and the receptors for insulin and IGF-1 are processed by a specific endoprotease that recognizes protein with extended basic sequences and resides in the trans-Golgi complex or in post-Golgi vesicles of the constitutive secretory pathway.

Publication types

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

MeSH terms

  • Acetylglucosaminidase
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Brefeldin A
  • Cells, Cultured
  • Cyclopentanes / pharmacology
  • Fluorescent Antibody Technique
  • Glycoside Hydrolases
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / immunology
  • Golgi Apparatus / metabolism*
  • Humans
  • Liver / immunology
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
  • Mice
  • Molecular Sequence Data
  • Molecular Weight
  • Neuraminidase
  • Protein Conformation
  • Rabbits
  • Rats
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*

Substances

  • Antibodies, Monoclonal
  • Cyclopentanes
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Immunologic
  • Brefeldin A
  • Glycoside Hydrolases
  • Neuraminidase
  • Acetylglucosaminidase
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase