Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment.
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.
Herz
J
J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Kowal
R C
RC
Goldstein
J L
JL
Brown
M S
MS
D000118:Acetylglucosaminidase; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D020126:Brefeldin A; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006026:Glycoside Hydrolases; D006056:Golgi Apparatus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009439:Neuraminidase; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003517:Cyclopentanes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D020126:Brefeldin A; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D000118:Acetylglucosaminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase