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

Research output: Contribution to journalArticle

198 Citations (Scopus)

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-terminaI 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 frans-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
StatePublished - 1990

Fingerprint

LDL-Receptor Related Proteins
LDL Receptors
Proteolysis
Golgi Apparatus
Lipoprotein Receptors
Insulin Receptor
Somatomedins
Processing
Molecular mass
Proteins
Brefeldin A
Membranes
Glycoside Hydrolases
Secretory Pathway
Membrane Glycoproteins
Neuraminidase
Cell Surface Receptors
Apolipoproteins E
Endoplasmic Reticulum
Lipoproteins

Keywords

  • LDL receptor
  • LRP
  • Secretory pathway
  • Trans-Golgi complex
  • Trans-golgi endoprotease

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

@article{03eda04515c4441e98ee34e99bfe9703,
title = "Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment",
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-terminaI 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 frans-Golgi complex or in post-Golgi vesicles of the constitutive secretory pathway.",
keywords = "LDL receptor, LRP, Secretory pathway, Trans-Golgi complex, Trans-golgi endoprotease",
author = "Joachim Herz and Kowal, {Robert C.} and Goldstein, {Joseph L.} and Brown, {Michael S.}",
year = "1990",
language = "English (US)",
volume = "9",
pages = "1769--1776",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment

AU - Herz, Joachim

AU - Kowal, Robert C.

AU - Goldstein, Joseph L.

AU - Brown, Michael S.

PY - 1990

Y1 - 1990

N2 - 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-terminaI 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 frans-Golgi complex or in post-Golgi vesicles of the constitutive secretory pathway.

AB - 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-terminaI 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 frans-Golgi complex or in post-Golgi vesicles of the constitutive secretory pathway.

KW - LDL receptor

KW - LRP

KW - Secretory pathway

KW - Trans-Golgi complex

KW - Trans-golgi endoprotease

UR - http://www.scopus.com/inward/record.url?scp=0025369190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025369190&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 1769

EP - 1776

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 6

ER -