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.
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
Robert A
RA
Orlando
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