A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched beta-VLDL in vitro

We report here the identification of a novel member of the low-density lipo protein receptor (the LDL receptor) family through signal sequence trap scr eening of a mouse lymphocyte cDNA library. The protein was termed LDL recep tor-related protein 9 (LRP9). LRP9 is a type I membrane protein predicted t o contain 696 amino acids with a calculated molecular mass of 74 764 Da. Th e NH2-terminal half of LRP9 contains two CUB domains separated by a single ligand-binding repeat. The second CUB domain is followed by a cluster of th ree additional ligand-binding repeats and a transmembrane domain. The COOH- terminal intracellular region contains a proline-rich region. LRP9 mRNA was expressed in the liver, kidney, lung, and heart at high levels, and in the spleen and brain at low levels. In situ hybridization analysis of mouse li ver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal lining cells, peritubular capillaries, choroid plexus, ependyma of the thi rd ventricle, pia matter, and hippocampus. In particular, high levels of ex pression were observed in the vascular walls. Apolipoprotein E (apoE)-enric hed beta -VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LR P9. These results raise the possibility that this newly identified receptor , which is expressed in the liver, may play a physiological role in the upt ake of apoE-containing lipoproteins.