VLDL receptors

VLDL receptor Loss-of-function (familial, autosomal recessive) Autosomal recessive cerebellar hypoplasia (ataxia, mental retardation)... 

RPE expresses several receptors responsible for lipoprotein uptake, including lipoprotein receptors LDL receptor (LDLR) (Tserentsoodol et al., 2006b), VLDL receptor (VLDLR) (Hu et al., 2008), as... 

The neural retina expresses several lipoprotein receptors including SR-BI, SR-BII (Tserentsoodol et al., 2006a,b), and VLDL receptor (VLDLR) (Hu et al., 2008). Thus, carotenoid flow through the RPE and further transport in the neural retina may also be mediated by lipoprotein receptors (Tserentsoodol et al., 2006a,b). SR-BI and SR-BII have been found to be localized mainly to the ganglion cell layer and POS in the monkey retina (Tserentsoodol et al., 2006a). 

VM Okun, R Moser, B Ronacher, E Kenndler, D Blaas. VLDL receptor fragments of different lengths bind to human rhino virus HRV2 with different stoichiometry—an analysis of virus-receptor complexes by capillary electrophoresis. J Biol Chem 276 1057-1062, 2001. 

Kozarsky, K.F., Jooss, K., Donahee, M., Strauss, J.F., III, Wilson, J.M. (1996). Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nature Genet., 13, 54—62. 

Cheon H. M., Seo S. J., Sun J., Sappington T. W. and Raikhel A. S. (2001) Molecular characterization of the VLDL receptor homolog mediating binding of lipophorin in oocyte of the mosquito Aedes aegypti. Insect Biochem. Mol. Biol. 31, 753-760. 

Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, Herz J (1999) Direct biding of Reehn to VLDL receptor tmd ApoE receptor 2 induces tyroene phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24 ... 

Homozygous VLDL receptor knockout mice are resistant to both genetic and diet-induced obesity caused by a decreased peripheral and whole-body uptake of NEFA with no alterations in eifher food intake or fat absorption [112]. The reduction in adipocyte TAG storage as shown by a decreased average fat cell size in VLDL receptor-deficient rodents implies an impaired FA delivery to adipose tissue in the absence of this lipoprotein receptor. Analogously, hepatic overexpression of hu-... 

J. P. Goudriann, P.J. Tacken, and V. E. Dahlmans, et ah. Protection from obesity in mice lacking the VLDL receptor, Arterioscler. Thromh. Vase. Biol., 2001, 23, 1488-1493. 

C-III, and phospholipids are transferred to EfDL. Apolipoproteins E and C-II are transferred to chylomicrons from EfDL and evenmally back through these metabolic events. Hepatic VLDL synthesis is regulated in part by diet and hormones and is inhibited by uptake of chylomicron remnants in the liver. VLDL is secreted from the Ever and serially converted via LPL to intermediate-density hpoprotein (IDL) and finally to LDL. VLDL receptors are found in adipose tissue and muscle and bear close homology to the structure of LDL receptors. 

The j8-VLDL receptor has been identified on mouse peritoneal macrophages [13,14], foam cells associated with rabbit aortic atherosclerotic plaques [58], and human monocyte-derived macrophages [14]. Although )8-VLDL can bind to LDL receptors, LDL do not compete with I-labeled jS-VLDL for uptake by mouse peritoneal macrophages [13,14], In addition, monocytes from LDL receptor-negative FH patients or from normal subjects express equivalent numbers of j8-VLDL receptors [14]. The j8-VLDL receptors thus are distinct from LDL receptors. The -VLDL receptor is also distinct from the receptors for chemically modified lipoproteins (see below). 

Macrophage yS-VLDL receptors may serve a back-up function in cholesterol clearance by facilitating removal of cholesterol-rich ]S-VLDL particles which accompany diet-induced hypercholesterolemia. When dog plasma cholesterol levels exceed 750 mg/dl, )8-VLDL accumulate in plasma and macrophages accumulate cholesterol and cholesterol esters [60]. The association of these events suggests that -VLDL may be taken up by macrophage j8-VLDL receptors for the deposition of plasma cholesterol esters. 

The only receptor-mediated uptake process regulated in macrophages involves suppression of )8-VLDL receptors. This suppression only occurs after extensive cholesterol ester accumulation and can be induced by either j8-VLDL or chemically modified LDL [13]. Lipoprotein uptake by all known receptor systems in macrophages causes a marked stimulation of ACAT activity which results in the massive accumulation of cholesteryl ester droplets in the cytoplasm [13]. Free cholesterol can be excreted from the macrophage if cholesterol-accepting Upoproteins such as HDL are present. The uncontrolled uptake and deposition of cholesteryl esters in macrophages is believed to be the key to formation of the foam cells which are associated with atherosclerosis. 

The so-called VLDL receptor a role in catabolism of VLDL . 566... 

VLDL receptor, apo E receptor type 2 (apoER2), and LRPl in signal transduction. 568... 

Subsequent to the realization that the VLDL receptor likely has only a limited role in lipoprotein metabolism, novel VLDL receptor functions have been uncovered. Elegant experimentation showed that it is involved in neuronal migration in the developing brain via binding of a ligand quite distinct from lipoproteins [6]. These important results are described in Section 5. However, there is a VLDL receptor, described in the following section, which indeed does deserve this name, since it has a very well defined function in lif)oprotein metabolism. 

A particularly interesting VLDL receptor homolog is that of the chicken (termed LDL receptor relative with eight binding repeats, or LR8 Fig. 4), because its functions are documented by both biochemical and genetic evidence. LR8 mediates a key step in the reproductive effort of the hen, that is, oocyte growth via deposition of yolk lipoproteins... 

Even high-density lipophorin, an abundant lipoprotein in the circulatory compartment of insects, is endocytosed in a variety of tissues via an LR8 homolog with very high similarity to the VLDL receptor/LR8 group [18] (N.R Dantuma, 1999). Presumably, binding of lipophorin to this receptor is mediated by apolipophorins I and II, which share sequence homology with mammalian apo B, and thus may behave similarly to the major yolk precursor proteins. 

Genetic models reveal new roles for apoERl and VLDL receptor in signal transduction... 

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