VLDL receptor
The very-low-density-lipoprotein receptor (VLDL-R) is a lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor. This receptor has been suggested to be important for the metabolism of apoprotein-E-containing triacylglycerol-rich lipoproteins, such as very-low-density-lipoprotein (VLDL), beta-migrating VLDL and intermediate-density lipoprotein. It is also one of the receptors of reelin, an extracellular matrix protein which regulates the processes of neuronal migration and synaptic plasticity. In humans, the VLDL-R is encoded by the VLDLR gene.[1]
Tissue distribution
In rabbits, the mRNA for the VLDLR was found to be most abundant in heart, skeletal muscle, and adipose tissue, but was not detectable in the liver. Human mRNA studies showed a very similar pattern of distribution. Hence, it has been suggested that the VLDLR might play an important role in the fatty acid metabolism of non-hepatic tissues.
Clinical signifance
A rare neurological disorder first described in the 1970s under the name "disequilibrium syndrome" is now considered to be caused by the disruption of VLDLR gene.[2] The disorder was renamed VLDLR-associated cerebellar hypoplasia (VLDLRCH) after a 2005 study.[3][4] It is associated with parental consanguinity and found in secluded communities such as the Hutterites. VLDLRCH is one of the two known genetic disorders caused by a disruption of reelin signaling pathway, along with Norman-Roberts syndrome.
References
- ^ Sakai J, Hoshino A, Takahashi S, Miura Y, Ishii H, Suzuki H, Kawarabayasi Y, Yamamoto T (January 1994). "Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene". J. Biol. Chem. 269 (3): 2173–82. PMID 8294473.
- ^ Moheb LA, Tzschach A, Garshasbi M et al. (February 2008). "Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome". Eur. J. Hum. Genet. 16 (2): 270–3. doi:10.1038/sj.ejhg.5201967. PMID 18043714. {
- ^ Boycott KM, Flavelle S, Bureau A et al. (2005). "Homozygous Deletion of the Very Low Density Lipoprotein Receptor Gene Causes Autosomal Recessive Cerebellar Hypoplasia with Cerebral Gyral Simplification". Am. J. Hum. Genet. 77 (3): 477–83. doi:10.1086/444400. PMC 1226212. PMID 16080122. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226212.
- ^ Online 'Mendelian Inheritance in Man' (OMIM) CEREBELLAR HYPOPLASIA, VLDLR-ASSOCIATED; VLDLRCH -224050
Further reading
- Oka K, Ishimura-Oka K, Chu MJ et al. (September 1994). "Mouse very-low-density-lipoprotein receptor (VLDLR) cDNA cloning, tissue-specific expression and evolutionary relationship with the low-density-lipoprotein receptor". Eur. J. Biochem. 224 (3): 975–82. doi:10.1111/j.1432-1033.1994.00975.x. PMID 7925422. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1994&volume=224&issue=3&spage=975.
- Ananyeva NM, Makogonenko YM, Kouiavskaia DV et al. (2008). "The binding sites for the very low density lipoprotein receptor and low-density lipoprotein receptor-related protein are shared within coagulation factor VIII". Blood Coagul. Fibrinolysis 19 (2): 166–77. doi:10.1097/MBC.0b013e3282f5457b. PMID 18277139.
- Ananyeva NM, Makogonenko YM, Sarafanov AG et al. (2008). "Interaction of coagulation factor VIII with members of the low-density lipoprotein receptor family follows common mechanism and involves consensus residues within the A2 binding site 484-509". Blood Coagul. Fibrinolysis 19 (6): 543–55. doi:10.1097/MBC.0b013e3283068859. PMID 18685438.
- Llorca J, Rodríguez-Rodríguez E, Dierssen-Sotos T et al. (2008). "Meta-analysis of genetic variability in the beta-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer's disease". Acta Neurol. Scand. 117 (1): 1–14. doi:10.1111/j.1600-0404.2007.00899.x. PMID 17854420.
- Ozcelik T, Akarsu N, Uz E et al. (2008). "Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans". Proc. Natl. Acad. Sci. U.S.A. 105 (11): 4232–6. doi:10.1073/pnas.0710010105. PMC 2393756. PMID 18326629. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2393756.
- Moheb LA, Tzschach A, Garshasbi M et al. (2008). "Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome". Eur. J. Hum. Genet. 16 (2): 270–3. doi:10.1038/sj.ejhg.5201967. PMID 18043714.
- Türkmen S, Hoffmann K, Demirhan O et al. (2008). "Cerebellar hypoplasia, with quadrupedal locomotion, caused by mutations in the very low-density lipoprotein receptor gene". Eur. J. Hum. Genet. 16 (9): 1070–4. doi:10.1038/ejhg.2008.73. PMID 18364738.
- Oganesian A, Armstrong LC, Migliorini MM et al. (2008). "Thrombospondins Use the VLDL Receptor and a Nonapoptotic Pathway to Inhibit Cell Division in Microvascular Endothelial Cells". Mol. Biol. Cell 19 (2): 563–71. doi:10.1091/mbc.E07-07-0649. PMC 2230579. PMID 18032585. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2230579.
- Boycott KM, Flavelle S, Bureau A et al. (2005). "Homozygous Deletion of the Very Low Density Lipoprotein Receptor Gene Causes Autosomal Recessive Cerebellar Hypoplasia with Cerebral Gyral Simplification". Am. J. Hum. Genet. 77 (3): 477–83. doi:10.1086/444400. PMC 1226212. PMID 16080122. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226212.
- Wruss J, Rünzler D, Steiger C et al. (2007). "Attachment of VLDL receptors to an icosahedral virus along the 5-fold symmetry axis: multiple binding modes evidenced by fluorescence correlation spectroscopy". Biochemistry 46 (21): 6331–9. doi:10.1021/bi700262w. PMID 17472347.
- Suzuki K, Nakamura K, Iwata Y et al. (2008). "Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients". Schizophr. Res. 98 (1–3): 148–56. doi:10.1016/j.schres.2007.09.029. PMID 17936586.
- Francis PJ, Hamon SC, Ott J et al. (2009). "Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss". J. Med. Genet. 46 (5): 300–7. doi:10.1136/jmg.2008.062737. PMID 19015224.
- Zhang G, Assadi AH, McNeil RS et al. (2007). Mueller, Ulrich. ed. "The Pafah1b Complex Interacts with the Reelin Receptor VLDLR". PLoS ONE 2 (2): e252. doi:10.1371/journal.pone.0000252. PMC 1800349. PMID 17330141. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1800349.
- Poirier S, Mayer G, Benjannet S et al. (2008). "The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2". J. Biol. Chem. 283 (4): 2363–72. doi:10.1074/jbc.M708098200. PMID 18039658.
- Crawford DC, Nord AS, Badzioch MD et al. (2008). "A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk". J. Lipid Res. 49 (3): 588–96. doi:10.1194/jlr.M700409-JLR200. PMID 18056683.
- Yamada Y, Ando F, Shimokata H (2005). "Association of polymorphisms in CYP17A1, MTP, and VLDLR with bone mineral density in community-dwelling Japanese women and men". Genomics 86 (1): 76–85. doi:10.1016/j.ygeno.2005.03.005. PMID 15953542.
- Chen Y, Hu Y, Lu K et al. (2007). "Very low density lipoprotein receptor, a negative regulator of the wnt signaling pathway and choroidal neovascularization". J. Biol. Chem. 282 (47): 34420–8. doi:10.1074/jbc.M611289200. PMID 17890782.
- Haines JL, Schnetz-Boutaud N, Schmidt S et al. (2006). "Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6". Invest. Ophthalmol. Vis. Sci. 47 (1): 329–35. doi:10.1167/iovs.05-0116. PMID 16384981.
- Sakai K, Tiebel O, Ljungberg MC et al. (2009). "A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of ApoE containing lipoproteins". Brain Res. 1276: 11–21. doi:10.1016/j.brainres.2009.04.030. PMC 2733343. PMID 19393635. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2733343.
- Moser R, Snyers L, Wruss J et al. (2005). "Neutralization of a common cold virus by concatemers of the third ligand binding module of the VLDL-receptor strongly depends on the number of modules". Virology 338 (2): 259–69. doi:10.1016/j.virol.2005.05.016. PMID 15950998.
External links