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 language | English (US) |
|---|---|
| Pages (from-to) | 1769-1776 |
| Number of pages | 8 |
| Journal | EMBO Journal |
| Volume | 9 |
| Issue number | 6 |
| State | Published - 1990 |
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Keywords
- LDL receptor
- LRP
- Secretory pathway
- Trans-Golgi complex
- Trans-golgi endoprotease
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment. / Herz, Joachim; Kowal, Robert C.; Goldstein, Joseph L.; Brown, Michael S.
In: EMBO Journal, Vol. 9, No. 6, 1990, p. 1769-1776.Research output: Contribution to journal › Article
}
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 -