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 lipoprotein receptor (the LDL receptor) family through signal sequence trap screening of a mouse lymphocyte cDNA library. The protein was termed LDL receptor-related protein 9 (LRP9). LRP9 is a type I membrane protein predicted to contain 696 amino acids with a calculated molecular mass of 74 764 Da. The NH(2)-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 three 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 liver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal lining cells, peritubular capillaries, choroid plexus, ependyma of the third ventricle, pia matter, and hippocampus. In particular, high levels of expression were observed in the vascular walls. Apolipoprotein E (apoE)-enriched beta-VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LRP9. These results raise the possibility that this newly identified receptor, which is expressed in the liver, may play a physiological role in the uptake of apoE-containing lipoproteins.
Sugiyama
T
T
Department of Hematopoietic Factors, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Kumagai
H
H
Morikawa
Y
Y
Wada
Y
Y
Sugiyama
A
A
Yasuda
K
K
Yokoi
N
N
Tamura
S
S
Kojima
T
T
Nosaka
T
T
Senba
E
E
Kimura
S
S
Kadowaki
T
T
Kodama
T
T
Kitamura
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D001057:Apolipoproteins E; D018076:DNA, Complementary; D026502:LDL-Receptor Related Proteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011973:Receptors, LDL; C102582:SORL1 protein, human; C491168:Sorl1 protein, mouse; C491167:Sorl1 protein, rat; C036053:VLDL receptor