Low density lipoprotein receptor gene family

The low density lipoprotein receptor gene family code for a class of structurally closely related cell surface receptors that fulfill diverse biological functions in different organs, tissues, and cell types.cite journal | author = Nykjaer A, Willnow TE | title = The low-density lipoprotein receptor gene family: a cellular Swiss army knife? | journal = Trends Cell Biol. | volume = 12 | issue = 6 | pages = 273–80 | year = 2002 | month = June | pmid = 12074887 | url = http://linkinghub.elsevier.com/retrieve/pii/S0962892402022821 | doi = 10.1016/S0962-8924(02)02282-1 ] The role that is most commonly associated with this evolutionarily ancient family is cholesterol homeostasis (maintenance of appropriate concentration of cholesterol). In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed in the liver by the endocytosis of the LDL receptor.cite journal | author = Li Y, Lu W, Marzolo MP, Bu G | title = Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates | journal = J. Biol. Chem. | volume = 276 | issue = 21 | pages = 18000–6 | year = 2001 | month = May | pmid = 11279214 | doi = 10.1074/jbc.M101589200 | url = ] Recent evidence indicates that the members of the LDL receptor gene family are active in the cell signalling pathways between specialized cells in many, if not all, multicellular organisms.cite journal | author = Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J | title = Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction | journal = J. Biol. Chem. | volume = 275 | issue = 33 | pages = 25616–24 | year = 2000 | month = August | pmid = 10827173 | doi = 10.1074/jbc.M000955200 | url = ] cite journal | author = Beffert U, Stolt PC, Herz J | title = Functions of lipoprotein receptors in neurons | journal = J. Lipid Res. | volume = 45 | issue = 3 | pages = 403–9 | year = 2004 | month = March | pmid = 14657206 | doi = 10.1194/jlr.R300017-JLR200 | url = ]

There are seven members of the LDLR family in mammals, namely:
* LDLR
* VLDL receptor (VLDLR)
* ApoER2, or LRP8
* Multiple epidermal growth factor (EGF) repeat-containing protein (MEGF7)
* LDLR-related protein 1
* LDLR-related protein 1b
* Megalin.

::See also: Soluble low density lipoprotein receptor-related protein (sLRP), whose impaired function is related to Alzheimer's Disease.

tructure

The members of the LDLR family are characterized by distinct functional domains present in characteristic numbers. These modules are:
* the "type A binding repeats" of 40 residues each, displaying a triple-disulfide-bond-stabilized negatively charged surface; certain head-to-tail combinations of these repeats are believed to specify ligand interactions;
* "type B repeats", also containing six cysteines each;
* EGF repeats with YWTD beta propeller domain;
* a transmembrane domain, and
* the cytoplasmic region with (a) signal(s) for receptor internalization via coated pits, containing the consensus tetrapeptide Asn-Pro-Xaa-Tyr (NPxY). This cytoplasmic tail controls both endocytosis and signaling by interacting with the phosphotyrosine binding (PTB) domain-containing proteins.

References

External links

* [http://www.jlr.org/cgi/content-nw/full/45/3/403/FIG1 Schematic representation of the seven mammalian LDL receptor (LDLR) family members]
* [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1635701&rendertype=figure&id=F1 LDL receptor family members]
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