Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteome.

TitleLow density lipoprotein receptor-related protein: regulation of the plasma membrane proteome.
Publication TypeJournal Article
Year of Publication2004
AuthorsGonias SL, Wu L, Salicioni AM
JournalThrombosis and haemostasis
Volume91
Issue6
Pagination1056-64
Date Published2004 Jun
ISSN0340-6245
KeywordsAnimals, Cell Membrane, Extracellular Matrix Proteins, Humans, Low Density Lipoprotein Receptor-Related Protein-1, Membrane Proteins, Proteome
AbstractProteins in the plasma membrane anchor the cell within its microenvironment and sense changes occurring outside the cell. The anchoring interactions are cell type-specific and may involve adjacent cells or extracellular matrix proteins (ECMPs). In development, wound healing, and in various forms of pathology, including thrombosis and atherosclerosis, the microenvironment of the cell may change rapidly and dramatically. How the cell responds is strongly dependent on the protein composition of its plasma membrane, which we refer to as the plasma membrane proteome. Processes that regulate the plasma membrane proteome may alter cellular response. Low density lipoprotein receptor-related protein-1 (LRP-1) is a member of the LDL receptor family; however, LRP-1 and other less well studied members of this gene family demonstrate multiple activities unrelated to lipid homeostasis. LRP-1 binds and internalizes numerous, structurally diverse ligands, delivering most but not all these ligands to lysosomes for degradation. The intracellular tail of LRP-1 binds signaling adaptor proteins and thus may function in cell signaling. Biological activities of LRP-1 include antigen presentation, phagocytosis, removal of apoptotic cells, and regulation of vascular permeability. This review focuses on an emerging view of LRP-1 activity, in which LRP-1 regulates the protein composition of the plasma membrane and thereby “models” or “landscapes” the cell surface. In some cases, plasma membrane modeling results from the binding to bifunctional ligands or intracellular adaptor proteins, so that LRP-1 is bridged to another plasma membrane protein and the entire complex undergoes endocytosis. Membrane proteins already known to be subject to this form of regulation include urokinase-type plasminogen activator receptor, amyloid precursor protein, tissue factor, and alpha(V)-containing integrins. LRP-1 also controls the plasma membrane proteome by regulating maturation and transport of proteins in the secretory pathway. At the same time, LRP-1 serves as a receptor for specific ECMPs, including fibronectin and thrombospondin. Although ECMP-binding to LRP-1 results in endocytosis and catabolism, these receptor-ligation events also may be coupled, directly or indirectly, to cell-signaling. Based on these novel activities, LRP-1 emerges as a protein capable of modeling the interface of the cell with its microenvironment.
DOI10.1267/THRO04061056
Alternate JournalThromb. Haemost.
PubMed ID15175790