The low-density lipoprotein receptor-related protein associates with calnexin, calreticulin, and protein disulfide isomerase in receptor-associated-protein-deficient fibroblasts.
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.
Orlando
Robert A
RA
Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico, Health Sciences Center, Albuquerque, NM 87131-5221, USA. rorlando@salud.unm.edu
D000818:Animals; D037281:Calnexin / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism*; D002478:Cells, Cultured; D005089:Exocytosis; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism*; D026563:LDL-Receptor Related Protein-Associated Protein / Q000235:genetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000032:analysis / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*
D037282:Calreticulin; D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D046911:Macromolecular Substances; D037281:Calnexin; D019704:Protein Disulfide-Isomerases