Document Detail

The low-density lipoprotein receptor-related protein associates with calnexin, calreticulin, and protein disulfide isomerase in receptor-associated-protein-deficient fibroblasts.
MedLine Citation:
PMID:  14980518     Owner:  NLM     Status:  MEDLINE    
The low-density lipoprotein receptor-related protein (LRP) is a large (>600 kDa) multi-ligand-binding cell surface receptor that is now known to participate in a diverse range of cellular events. To accomplish this diverse role, LRP is composed of repetitive amino acid motifs consisting of complement-type and EGF precursor-type repeats. Within these repeats are six conserved cysteine residues that form the core disulfide bond structure of each repeat. To accommodate the intricate folding that such a complex structure dictates, a specialized chaperone is present in the endoplasmic reticulum (ER) called the receptor-associated protein (RAP) that binds to LRP immediately following its biosynthesis and assists in its exocytic transport. Interestingly, RAP -/- mice show reduced LRP expression in certain cell types, but not a more global affect on LRP expression that was expected. Such a tissue-restricted effect by RAP prompted an investigation if other ER chaperones associate with LRP to assist in its complex folding requirements and compensate for the absence of RAP in RAP -/- cells. Fibroblasts obtained from RAP -/- mice demonstrate similar LRP expression levels and subcellular distribution as RAP +/+ fibroblasts. Moreover, RAP -/- cells show an identical exocytic trafficking rate for LRP as RAP +/+ cells and comparable cell surface internalization kinetics. In RAP -/- cells, three well-known ER chaperones, calnexin, calreticulin, and protein disulfide isomerase (PDI), associate with LRP and likely compensate for the absence of RAP.
Robert A Orlando
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  294     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-24     Completed Date:  2004-03-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  244-53     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Health Sciences Center, Albuquerque, NM 87131-5221, USA.
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MeSH Terms
Calnexin / metabolism*
Calreticulin / metabolism*
Cells, Cultured
Fibroblasts / chemistry,  metabolism*
LDL-Receptor Related Protein 1 / analysis,  metabolism*
LDL-Receptor Related Protein-Associated Protein / genetics
Macromolecular Substances
Mice, Knockout
Protein Disulfide-Isomerases / metabolism*
Grant Support
Reg. No./Substance:
0/Calreticulin; 0/LDL-Receptor Related Protein 1; 0/LDL-Receptor Related Protein-Associated Protein; 0/Macromolecular Substances; 139873-08-8/Calnexin; EC Disulfide-Isomerases

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