LRPAP1

LRPAP1 Full Name

low density lipoprotein receptor-related protein associated protein 1

LRPAP1 Introduction

Low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1), also known as α2-macroglobulin receptor-associated protein (A2MRAP) or RAP, is an endoplasmic reticulum–resident chaperone protein that plays an essential role in the maturation and trafficking of members of the LDL receptor family. Ubiquitously expressed, it is most abundant in the liver, brain and vascular cells. LRPAP1 is involved in the folding and intracellular trafficking of large endocytic receptors such as LRP1, LRP2 (megalin) and other LDLR-related proteins. LRPAP1 is primarily involved in the secretory pathway to transport these receptors to the cell surface in a competent form and prevent premature ligand binding in the ER.

Figure 1. Low-density lipoprotein receptor related protein (LRP) may modulate platelet-derived growth factor-mediated signaling pathways.(Source: Lillis AP, et al.; 2005)

Mechanistically, LRPAP1 regulates receptor–ligand interactions through competition with ligand binding to LRP family members during the production and trafficking of the receptors. This inhibitory effect prevents misfolding or degradation of the receptor and allows for receptor recycling. As a consequence, indirectly, most of the above biological functions are affected in this manner, such as lipid homeostasis, endocytosis of multiple ligands, uptake of neurotrophic factors, transport of vitamins and hormones, and clearance of proteases and extracellular signalling proteins. LRPAP1 is involved in multiple signalling cascades in pathways linked to metabolism, neuronal maintenance, and vascular homeostasis, most probably by regulating the availability of these receptors at the cell surface.

Modifications in LRPAP1 expression and/or function have been associated with several pathological conditions. Variants in LRPAP1 have been identified as genetic factors underlying myopia and high myopia. It has been postulated that these diseases arise due to the defective trafficking of extracellular matrix remodeling receptors in ocular tissues. Alterations in the LRPAP1-mediated trafficking of receptors have also been shown to contribute to neurodegenerative diseases such as Alzheimer's disease. In this condition, a decrease in LRP1 function leads to reduced clearance of amyloid-β from the brain. Changes in LRPAP1 could also contribute to lipid and protein metabolism defects that underlie vascular pathology and metabolic disease. The importance of LRPAP1 in regulating the activity of LRP-family receptors has now positioned this protein as a key molecular link between receptor function and neuronal, metabolic and degenerative disease.

Alternate Names for LRPAP1

LRPAP1; low density lipoprotein receptor-related protein associated protein 1; A2MRAP,low density lipoprotein related protein associated protein 1 (alpha 2 macroglobulin receptor associated protein 1); alpha-2-macroglobulin receptor-associated protein; HB

• 1.Lillis AP, et al.; Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability. J Thromb Haemost. 2005, 3(8):1884-93.