Disease relevance of VLDLR

• The receptor gene is located on the avian sex chromosome Z, in agreement with the sex linkage of a single-gene defect in animals that fail to reproduce because of the lack of expression of functional VLDL/VTGR [1].
• Mutations in a chicken homolog of VLDL-R cause female sterility and premature atherosclerosis [2].
• This receptor is not expressed in liver tissue; however, transgenic expression of VLDL-R in liver corrects hypercholesterolemia in experiment animals, which suggests that it can be a candidate for gene therapy for various hyperlipidemias [2].
• Screening of a phage library displaying single chain fragments of the variable regions of human immunoglobulins (scFv) for binding to the ovarian chicken very low-density lipoprotein/vitellogenin receptor (OVR) led to the isolation of several antibody fragments with high affinity [3].

High impact information on VLDLR

• In situ hybridization analysis of oocytes suggested that VLDL/VTGR mRNA may relocalize during oocyte growth [1].
• Here we describe a naturally occurring mutation in a VLDLR that causes a dramatic abnormal phenotype [4].
• Furthermore, the chicken vitellogenin receptor, which also binds apolipoproteins receptor (LDLR) superfamily [Bujo, H., Hermann, M., Kaderli, M. O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T. & Schneider, W. J. (1994) EMBO J. 13, 5165-5175] [5].
• In addition to these biochemical and immunological lines of evidence for the identity of the vitellogenin receptor with the very low density lipoprotein receptor, genetic proof was obtained [6].
• Cross-reactivity, at the level of ligand recognition, was observed between quail and chicken VLDL/vitellogenin receptors, and immunological relatedness was demonstrated by Western blotting with a rabbit anti-chicken oocyte VLDL receptor antibody [7].

Biological context of VLDLR

• The latter is essential for female reproduction, because a naturally occurring point mutation in the gene encoding the short form of the VLDLR causes its functional absence, resulting in atherosclerosis and a general failure to lay eggs [8].
• The deduced amino acid sequence was 72% homologous to the chicken VLDL/VTG receptor, and the characteristic domains were highly conserved [9].

Anatomical context of VLDLR

• Two splice variant forms of the chicken very low density lipoprotein receptor (VLDLR) have recently been shown to exist in both male and female chicken gonads [8].
• This phenotype results from a point mutation in the gene specifying the very low density lipoprotein receptor (VLDLR), whose protein product normally mediates the massive oocytic uptake of egg yolk precursors from the circulation [10].

Associations of VLDLR with chemical compounds

• The mutation converts a cysteine residue into a serine, resulting in an unpaired cysteine and greatly reduced expression of the mutant avian VLDLR on the oocyte surface [4].
• Two known estrogen-induced ligands of the oocyte-specific 95-kDa very low density lipoprotein/vitellogenin receptor (OVR) are also fragmented by yolk cathepsin D (Retzek, H., Steyrer, E., Sanders, E. J., Nimpf, J., and Schneider, W. J. (1992) DNA Cell Biol. 11, 661-672) [11].

Analytical, diagnostic and therapeutic context of VLDLR

• Western blotting (immunoblotting) of the laying hen 95-kDa receptor with polyclonal rabbit anti-chicken oocyte VLDL receptor IgG resulted in an ECL signal with the same position of migration as that observed in ligand blots using biotinylated plasma and yolk VLDL [12].

References