A NEW LOW-DENSITY-LIPOPROTEIN RECEPTOR HOMOLOG WITH 8 LIGAND-BINDING REPEATS IN BRAIN OF CHICKEN AND MOUSE

The blood-brain barrier necessitates disparate macromolecular transpor t systems in the brain and central nervous system. We now report the d iscovery of a new member of the low density lipoprotein receptor (LDLR ) family whose expression is highly restricted to the brain. The full- length cDNA specifying the chicken receptor (open reading frame, 2754 base pairs) as well as a cDNA for the major portion of its murine homo logue have been obtained, The novel receptor shows the greatest simila rity to the group of LDLR relatives with 8 ligand binding repeats, in chicken termed LR8 and in mammals, very low density lipoprotein recept ors. Thus, in addition to 8 tandemly arranged ligand binding repeats, the five-domain receptor contains an O-linked sugar region and the int ernalization signal, Phe-Asp-Asn-Pro-Val-Tyr, typical for all LDLR gen e family members, In chicken, the 6.5-kb receptor transcript is presen t at high levels in brain and at much lower levels in extraoocytic cel ls of the ovary; in mouse, the same transcript of 6.5 kb was detected in brain, but not in heart (the major site of very low density lipopro tein receptor expression), lung, liver, kidney, and ovary. An antibody directed against the predicted carboxyl terminus of the avian recepto r detected a 130-kDa protein in brain extracts. The apparent size of t he immunoreactive protein is compatible with extensive glycosylation o f the 894-residue mature form of the receptor. The presence of this no vel receptor in brain of a bird and a rodent suggests an important and evolutionary conserved function.