Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability

The low-density lipoprotein (LDL) receptor related protein (LRP1 or LRP) is a large endocytic receptor widely expressed in several tissues and known to play roles in areas as diverse as lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. This member of the LDL receptor superfamily is constitutively endocytosed from the membrane and recycled back to the cell surface. Its many functions were long thought to involve its ability to bind over 30 different ligands and deliver them to lysosomes for degradation. However, LRP has since been shown to interact with scaffolding and signaling proteins via its intracellular domain in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. This multi-talented receptor has been implicated in regulation of platelet derived growth factor receptor activity, integrin maturation and recycling, and focal adhesion disassembly. These functions may account for recent studies identifying LRP's role in protection of the vasculature, regulation of cell migration, and modulation of the integrity of the blood-brain barrier.