Low‐density Lipoprotein Receptor (LDLR) Family: Genetics and Evolution

Abstract

The low‐density lipoprotein receptor family comprises a large and growing number of genes, whose products contain a characteristic set of structural domains. Attempts to delineate the evolutionary history of this gene family must take into consideration newly discovered functions, ranging from ligand binding by the extracellular domains to signal transduction through the cytoplasmic regions of the receptors.

Keywords: low‐density lipoprotein; gene family; receptor; ligand binding; signal transduction

References

Brandes C, Kahr L, Stockinger W et al. (2001) Alternative splicing in the ligand binding domain of mouse ApoE receptor‐2 produces receptor variants binding reelin but not α2‐macroglobulin. Journal of Biological Chemistry 276: 22160–22169.

Bujo H, Yamamoto T, Hayashi K et al. (1995) Mutant oocytic LDL receptor gene family member causes atherosclerosis and female sterility. Proceedings of the National Academy of Sciences of the United States of America 92: 9905–9909.

Goldstein JL, Brown MS, Anderson RG, Russell DW and Schneider WJ (1985) Receptor‐mediated endocytosis: concepts emerging from the LDL receptor system. Annual Reviews in Cell Biology 1: 1–39.

Hampe W, Rezgaoui M, Hermans‐Borgmeyer I and Schaller HC (2001) The genes for the human VPS10 domain‐containing receptors are large and contain many small exons. Human Genetics 108: 529–536.

Liu CX, Musco S, Lisitsina NM, Yaklichkin SY and Lisitsyn NA (2000) Genomic organization of a new candidate tumor suppressor gene, LRP1B. Genomics 69: 271–274.

Mahon MG, Lindstedt KA, Hermann M, Nimpf J and Schneider WJ (1999) Multiple involvement of clusterin in chicken ovarian follicle development. Binding to two oocyte‐specific members of the low density lipoprotein receptor gene family. Journal of Biological Chemistry 274: 4036–4044.

Sappington TW and Raikhel AS (1998) Ligand‐binding domains in vitellogenin receptors and other LDL‐receptor family members share a common ancestral ordering of cysteine‐rich repeats. Journal of Molecular Evolution 46: 476–487.

Takahashi S, Kawarabayasi Y, Nakai T, Sakai J and Yamamoto T (1992). Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor‐like protein with distinct ligand specificity. Proceedings of the National Academy of Sciences of the United States of America 89: 9252–9256.

Willnow TE, Nykjaer A and Herz J (1999) Lipoprotein receptors: new roles for ancient proteins. Nature Cell Biology 1: E157–E162.

Yamazaki H, Bujo H, Kusunoki J et al. (1996) Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member. Journal of Biological Chemistry 271: 24761–24768.

Further Reading

Boucher P, Liu P, Gotthardt M et al. (2002) PDGF mediates tyrosine phosphorylation of the cytoplasmic domain of the LDL receptor‐related protein (LRP) in caveolae. Journal of Biological Chemistry 19: 19.

Bujo H, Hermann M, Kaderli MO et al. (1994) Chicken oocyte growth is mediated by an eight ligand binding repeat member of the LDL receptor family. EMBO Journal 13: 5165–5175.

Fagundes NJ, Salzano FM, Batzer MA, Deininger PL and Bonatto SL (2005) Worldwide genetic variation at the 3′‐UTR region of the LDLR gene: possible influence of natural selection. Annals of Human Genetics 69: 389–400.

Kass DH, Knight A and Deininger PL (2004) Evolution of a hypervariable region of the low density lipoprotein receptor (LDLR) gene in humans and other hominoids. Genetica 121: 187–193.

Loukinova E, Ranganathan S, Kuznetsov S et al. (2002) PDGF‐induced tyrosine phosphorylation of the LDL receptor‐related protein (LRP): evidence for integrated co‐receptor function between LRP and the PDGF receptor. Journal of Biological Chemistry 19: 19.

Nimpf J and Schneider WJ (1998) The VLDL receptor: an LDL receptor relative with eight ligand binding repeats, LR8. Atherosclerosis 141: 191–202.

Wang QF, Prabhakar S, Wang Q et al. (2006) Primate‐specific evolution of an LDLR enhancer. Genome Biology 7: R68.

Willnow TE, Nykjaer A and Herz J (1999) Lipoprotein receptors: new roles for ancient proteins. Nature Cell Biology 1: E157– E162.

Web Links

Low density lipoprotein receptor (LDLR); LocusID: 3949. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3949

Low density lipoprotein receptor (LDLR); MIM number: 606945. MIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim=606945

Low density lipoprotein‐related protein 1 (LRP1); LocusID: 4035. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4035

Low density lipoprotein‐related protein 1 (LRP1); MIM number: 107770. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim=107770

Sortilin‐related receptor, L (SORL1); LocusID: 6653. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6653

Sortilin‐related receptor, L (SORL1); MIM number: 602005. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?

The low density lipoprotein receptor (LDLR) gene in familial hypercholesterolemia. [Comprehensive information about LDLR mutations.] http://www.ucl.ac.uk/fh/

Very low density lipoprotein receptor (VLDLR); LocusID: 7436. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7436

Very low density lipoprotein receptor (VLDLR); MIM number: 192977. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?192977

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How to Cite close
Schneider, Wolfgang Johann(Apr 2008) Low‐density Lipoprotein Receptor (LDLR) Family: Genetics and Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006138.pub2]