LDL receptor-related protein 1 and its interacting partners in tissue homeostasis.

Abstract

LDL receptor-related protein 1 (LRP1) is a multifunctional protein with endocytic and signal transduction properties due to its interaction with numerous extracellular ligands and intracellular proteins. This brief review highlights key developments in identifying novel functions of LRP1 in liver, lung, and the central nervous system in disease pathogenesis. In hepatocytes, LRP1 complexes with phosphatidylinositol 4-phosphate 5-kinase-1 and its related protein to maintain intracellular levels of phosphatidylinositol (4,5) bisphosphate and preserve lysosome and mitochondria integrity. In contrast, in smooth muscle cells, macrophages, and endothelial cells, LRP1 interacts with various different extracellular ligands and intracellular proteins in a tissue-dependent and microenvironment-dependent manner to either enhance or suppress inflammation, disease progression or resolution. Similarly, LRP1 expression in astrocytes and oligodendrocyte progenitor cells regulates cell differentiation and maturation in a developmental-dependent manner to modulate neurogenesis, gliogenesis, and white matter repair after injury. LRP1 modulates metabolic disease manifestation, inflammation, and differentiation in a cell-dependent, time-dependent, and tissue-dependent manner. Whether LRP1 expression is protective or pathogenic is dependent on its interaction with specific ligands and intracellular proteins, which in turn is dependent on the cell type and the microenvironment where these cells reside.