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

Research output: Contribution to journalArticle

201 Scopus citations

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 ~ 515 and 85 kd respectively. The larger NH2-terminal α-subunit lacks a membrane-spanning region. It remains attached to the membrane through noncovalent association with the smaller COOH terminal β-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.

Original languageEnglish (US)
Pages (from-to)1769-1776
Number of pages8
JournalEMBO Journal
Volume9
Issue number6
DOIs
StatePublished - 1990

Keywords

  • LDL receptor
  • LRP
  • secretory pathway
  • trans-Golgi complex
  • trans-Golgi endoprotease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment'. Together they form a unique fingerprint.

  • Cite this