Structure and Function of the Lipolysis Stimulated Lipoprotein Receptor

Stenger, Christophe; Corbier, Catherine; Yen, Frances T

doi:10.5772/34657

Cited by 5 publications

(8 citation statements)

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“…Lsr is made of 10 exons with three different splice variants: α, α′, and β ( Yen et al, 2008 ; Stenger et al, 2012a ). The α splice variant translates a full-length protein that has an external C terminus, a transmembrane domain, and a cytoplasmic N-terminal tail.…”

Section: Resultsmentioning

confidence: 99%

“…More recently, in epithelial cells, Lipolysis-stimulated lipoprotein receptor (LSR) was described as a tricellular TJ protein required to recruit tricellulin to the epithelial tricellular TJs ( Masuda et al, 2011 ). LSR contains an extracellular N-terminal Ig domain followed by a single transmembrane region and a cytoplasmic C-terminal tail ( Stenger et al, 2012a ). The original role of the protein was described in lipid metabolism studies, as LSR was first discovered to be expressed in hepatocytes, where it plays a role in the clearance of triglyceride-rich lipoproteins and low-density lipoproteins, and also acts as a apolipoprotein B/E–containing lipoprotein receptor ( Stenger et al, 2012a ).…”

Section: Introductionmentioning

confidence: 99%

“…LSR contains an extracellular N-terminal Ig domain followed by a single transmembrane region and a cytoplasmic C-terminal tail ( Stenger et al, 2012a ). The original role of the protein was described in lipid metabolism studies, as LSR was first discovered to be expressed in hepatocytes, where it plays a role in the clearance of triglyceride-rich lipoproteins and low-density lipoproteins, and also acts as a apolipoprotein B/E–containing lipoprotein receptor ( Stenger et al, 2012a ). Lsr knockout mice die before embryonic day 15.5 (E15.5), but the cause of death remains unclear ( Mesli et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation

Sohet

Lin

Munji

et al. 2015

Journal of Cell Biology

116

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation

Sohet

Lin

Munji

et al. 2015

Journal of Cell Biology

116

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show abstract

“…shown to play a role in the removal of TG-rich lipoproteins during the postprandial phase. 16,17 Although the absence of both LSR alleles is embryonic lethal, studies on the heterozygous LSR +/− mouse revealed that reduced levels of LSR lead to elevated postprandial lipemia, moderate hypercholesterolemia and hypertriglyceridemia. 16 When placed on high-fat cholesterol-containing Western diet, atherogenic lipoproteins such as LDL and TG-rich lipoproteins accumulate in the plasma of LSR +/− mice, accompanied by increased lipid deposits in the aorta.…”

Section: The Lipolysis Stimulated Lipoprotein Receptor (Lsr) Has Beenmentioning

confidence: 99%

“…The lipolysis stimulated lipoprotein receptor (LSR) has been shown to play a role in the removal of TG‐rich lipoproteins during the postprandial phase . Although the absence of both LSR alleles is embryonic lethal, studies on the heterozygous LSR +/− mouse revealed that reduced levels of LSR lead to elevated postprandial lipemia, moderate hypercholesterolemia and hypertriglyceridemia .…”

Section: Introductionmentioning

confidence: 99%

Effect of LSR polymorphism on blood lipid levels and age‐specific epistatic interaction with the APOE common polymorphism

et al. 2018

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The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low-density lipoprotein levels (β: .114, P: .777 × 10 , β: .125, P: .639 × 10 , β: .059, P: .531 × 10 , respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.

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Lactoferrin and its hydrolysate bind directly to the oleate‐activated form of the lipolysis stimulated lipoprotein receptor

et al. 2012

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The hepatic removal of triglyceride-rich chylomicrons during the postprandial phase represents an important step towards determining the bioavailability of dietary lipids amongst the peripheral tissues. Indeed, elevated postprandial lipemia is often associated with obesity and increased risk of coronary heart disease. The milk protein, lactoferrin, has been shown to inhibit hepatic chylomicron remnant removal by the liver, resulting in increased postprandial lipemia. Despite numerous studies on potential targets for lactoferrin, the molecular mechanisms underlying the effect of lactoferrin remain unclear. We recently demonstrated that the lipolysis stimulated lipoprotein receptor (LSR) contributes to the removal of triglyceride-rich lipoproteins during the postprandial phase. Here, we report that while lactoferrin does not have any significant effect on LSR protein levels in mouse Hepa1-6 cells, this protein colocalizes with LSR in cells but only in the presence of oleate, which is needed to obtain LSR in its active form as lipoprotein receptor. Ligand blotting using purified LSR revealed that lactoferrin binds directly to the receptor in the presence of oleate and prevents the binding of triglyceride-rich lipoproteins. Both C-and N-lobes of lactoferrin as well as a mixture of peptides derived from its hydrolysis retained the ability to bind LSR in its active form. We propose then that the elevated postprandial lipemia observed upon lactoferrin treatment in vivo is mediated in part by its direct interaction with free fatty acid activated LSR, thus preventing clearance of chylomicrons and their remnants through the LSR pathway. Abbreviations apoE, apolipoprotein E; FFA, free fatty acid; HPRT, hypoxanthine guanine phosphoribosyltransferase; LDL, low-density lipoprotein; LDL-R, LDL receptor; Lf, lactoferrin; LRP, LDL-R-related protein; LSR, lipolysis stimulated lipoprotein receptor; TG, triglyceride; VLDL, very-low-density lipoprotein.

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Structure and Function of the Lipolysis Stimulated Lipoprotein Receptor

Cited by 5 publications

References 77 publications

LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation

LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation

Effect of LSR polymorphism on blood lipid levels and age‐specific epistatic interaction with the APOE common polymorphism

Lactoferrin and its hydrolysate bind directly to the oleate‐activated form of the lipolysis stimulated lipoprotein receptor

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