Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface.

TitleLow density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface.
Publication TypeJournal Article
Year of Publication2004
AuthorsSalicioni AM, Gaultier A, Brownlee C, Cheezum MK, Gonias SL
JournalThe Journal of biological chemistry
Volume279
Issue11
Pagination10005-12
Date Published2004 Mar 12
ISSN0021-9258
KeywordsAnimals, Antigens, CD29, Biological Transport, Cell Adhesion, Cell Line, Cell Membrane, Cells, Cultured, CHO Cells, Cricetinae, Densitometry, Dose-Response Relationship, Drug, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Endocytosis, Endoplasmic Reticulum, Fibronectins, Glycoside Hydrolases, Humans, Immunoblotting, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Time Factors
AbstractLow density lipoprotein receptor-related protein-1 (LRP-1) mediates the endocytosis of multiple plasma membrane proteins and thereby models the composition of the cell surface. LRP-1 also functions as a catabolic receptor for fibronectin, limiting fibronectin accumulation in association with cells. The goal of the present study was to determine whether LRP-1 regulates cell surface levels of the beta(1) integrin subunit. We hypothesized that LRP-1 may down-regulate cell surface beta(1) by promoting its internalization; however, unexpectedly, LRP-1 expression was associated with a substantial increase in cell surface beta(1) integrin in two separate cell lines, murine embryonic fibroblasts (MEFs) and CHO cells. The total amount of beta(1) integrin was unchanged because LRP-1-deficient cells retained increased amounts of beta(1) in the endoplasmic reticulum (ER). Expression of human LRP-1 in LRP-1-deficient MEFs reversed the shift in subcellular beta(1) integrin distribution. Metabolic labeling experiments demonstrated that the precursor form of newly synthesized beta(1) integrin (p105) is converted into mature beta(1) (p125) more slowly in LRP-1-deficient cells. Although low levels of cell surface beta(1) integrin, in LRP-1-deficient MEFs, were associated with decreased adhesion to fibronectin, the subcellular distribution of beta(1) integrin was most profoundly dependent on LRP-1 only after the cell cultures became confluent. A mutagen-treated CHO cell line, in which LRP-1 is expressed but retained in the secretory pathway, also demonstrated nearly complete ER retention of beta(1) integrin. These studies support a model in which LRP-1 either directly or indirectly promotes maturation of beta(1) integrin precursor and thereby increases the level of beta(1) integrin at the cell surface.
DOI10.1074/jbc.M306625200
Alternate JournalJ. Biol. Chem.
PubMed ID14699139