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VLDLR  -  very low density lipoprotein receptor

Gallus gallus

 
 
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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

  1. Chicken oocyte growth is mediated by an eight ligand binding repeat member of the LDL receptor family. Bujo, H., Hermann, M., Kaderli, M.O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T., Schneider, W.J. EMBO J. (1994) [Pubmed]
  2. The mammalian low-density lipoprotein receptor family. Hussain, M.M., Strickland, D.K., Bakillah, A. Annu. Rev. Nutr. (1999) [Pubmed]
  3. Preferential recognition of the very low-density lipoprotein receptor ligand binding site by antibodies from phage display libraries. Pfistermueller, D.M., Blaas, D., Hodits, R.A. FEBS Lett. (1996) [Pubmed]
  4. Mutant oocytic low density lipoprotein receptor gene family member causes atherosclerosis and female sterility. Bujo, H., Yamamoto, T., Hayashi, K., Hermann, M., Nimpf, J., Schneider, W.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. The Drosophila yolkless gene encodes a vitellogenin receptor belonging to the low density lipoprotein receptor superfamily. Schonbaum, C.P., Lee, S., Mahowald, A.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. A single chicken oocyte plasma membrane protein mediates uptake of very low density lipoprotein and vitellogenin. Stifani, S., Barber, D.L., Nimpf, J., Schneider, W.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  7. Characterization of the Japanese quail oocyte receptor for very low density lipoprotein and vitellogenin. Elkin, R.G., MacLachlan, I., Hermann, M., Schneider, W.J. J. Nutr. (1995) [Pubmed]
  8. Assessment of reproductive function in mutant restricted ovulator carrier roosters. Elkin, R.G., Zhong, Y. Poult. Sci. (2002) [Pubmed]
  9. cDNA cloning and expression of the Xenopus laevis vitellogenin receptor. Okabayashi, K., Shoji, H., Nakamura, T., Hashimoto, O., Asashima, M., Sugino, H. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  10. Validation of a modified PCR-based method for identifying mutant restricted ovulator chickens: substantiation of genotypic classification by phenotypic traits. Elkin, R.G., Zhong, Y., Porter, R.E., Walzem, R.L. Poult. Sci. (2003) [Pubmed]
  11. The chicken oocyte receptor for lipoprotein deposition recognizes alpha 2-macroglobulin. Jacobsen, L., Hermann, M., Vieira, P.M., Schneider, W.J., Nimpf, J. J. Biol. Chem. (1995) [Pubmed]
  12. Visualization of the chicken oocyte lipoprotein receptor by ligand blotting with biotinylated plasma and yolk very low density lipoproteins. Elkin, R.G., Schneider, W.J. Poult. Sci. (1994) [Pubmed]
 
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