A new low density lipoprotein receptor homologue with 8 ligand binding repeats in brain of chicken and mouse

Abstract

The blood-brain barrier necessitates disparate macromolecular transport systems in the brain and central nervous system. We now report the discovery 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 homologue have been obtained. The novel receptor shows the greatest similarity to the group of LDLR relatives with 8 ligand binding repeats, in chicken termed LR8 and in mammals, very low density lipoprotein receptors. Thus, in addition to 8 tandemly arranged ligand binding repeats, the five-domain receptor contains an O-linked sugar region and the internalization signal, Phe-Asp-Asn-Pro-Val-Tyr, typical for all LDLR gene family members. In chicken, the 6.5-kb receptor transcript is present at high levels in brain and at much lower levels in extraoocytic cells 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 lipoprotein receptor expression), lung, liver, kidney, and ovary. An antibody directed against the predicted carboxyl terminus of the avian receptor detected a 130- kDa protein in brain extracts. The apparent size of the immunoreactive protein is compatible with extensive glycosylation of the 894-residue mature form of the receptor. The presence of this novel receptor in brain of a bird and a rodent suggests an important and evolutionary conserved function.