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A gene for a low density lipoprotein receptor-related protein in the nematode Caenorhabditis elegans.

ABSTRACT: A >23-kb gene that encodes a large integral membrane protein with a predicted structure similar to that of the low density lipoprotein (LDL) receptor-related protein (LRP) of mammals has been isolated and sequenced from the free-living nematode Caenorhabditis elegans. The 4753-amino acid predicted C. elegans product shares a nearly identical number and arrangement of amino acid sequence motifs with human LRP, and several exons of the C. elegans LRP gene correspond to exons of related parts of the human LDL receptor gene. The existence of an apparent homolog of LRP in C. elegans offers the possibility of genetic analysis of the in vivo roles of LRP and of the relationship between protein structure and function in a simple model organism.

SUBMITTER: Yochem J

PROVIDER: S-EPMC46554 | biostudies-other | 1993 May

REPOSITORIES: biostudies-other

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A gene for a low density lipoprotein receptor-related protein in the nematode Caenorhabditis elegans.

Yochem J J Greenwald I I

Proceedings of the National Academy of Sciences of the United States of America 19930501 10

A >23-kb gene that encodes a large integral membrane protein with a predicted structure similar to that of the low density lipoprotein (LDL) receptor-related protein (LRP) of mammals has been isolated and sequenced from the free-living nematode Caenorhabditis elegans. The 4753-amino acid predicted C. elegans product shares a nearly identical number and arrangement of amino acid sequence motifs with human LRP, and several exons of the C. elegans LRP gene correspond to exons of related parts of th ...[more]

PMID: 8506301

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Retinal gene expression of low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice

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Retinal gene expression of low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice

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Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1.

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Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

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| S-EPMC5007848 | biostudies-literature

Low-density lipoprotein receptor-related protein 6 regulates alternative pre-mRNA splicing.

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Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis.

Project description:Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood.

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Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

Project description:Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH)(2)D(3). In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591). BMD values at the lumbar spine 1-4 (L1-4) and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs) in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population.

| S-EPMC3235174 | biostudies-literature

Genetic analysis of the relationship between bone mineral density and low-density lipoprotein receptor-related protein 5 gene polymorphisms.

Project description:BackgroundA number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.MethodsPublished literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.ResultsA total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02 g/cm², 95% CI = 0.01-0.03, P < 10⁻⁴; at femur neck (FN): WMD = 0.01 g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02 g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02 g/cm², 95% CI = 0.02-0.03, P < 10⁻⁵; WMD at FN = 0.01 g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03 g/cm², 95% CI = 0.01-0.05, P = 0.005).ConclusionThis meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.

| S-EPMC3871666 | biostudies-literature

A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density in Japanese male workers.

Project description:ObjectivesBoth genetic and lifestyle factors have been shown to influence bone mineral density (BMD). We investigated the correlations between BMD and low-density lipoprotein receptor-related protein 5 (LRP5) A1330V (rs3736228) polymorphism, exercise, smoking, and alcohol intake in Japanese male workers.MethodsThe subjects were 829 male employees (aged 20-59 years) of a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual-energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time, and genomic DNA was isolated from peripheral leukocytes.ResultsMean ± standard deviation (SD) BMD was 0.557 ± 0.059 g/cm(2). The genotype frequencies of LRP5 gene polymorphism were 51, 42, and 7% for AA, AV, and VV, respectively. Analysis of variance and post hoc Tukey test indicated that mean BMD was significantly lower in subjects with VV genotype than in those with AA genotype (0.540 ± 0.048 versus 0.562 ± 0.062 g/cm(2)). According to multiple linear regression analysis, LRP5 A1330V polymorphism was an independent determinant of BMD, after adjusting for age, body mass index (BMI), and lifestyle variables. Exercise (past or current) also influenced BMD.ConclusionsThese findings suggest that LRP5 A1330V polymorphism and exercise may influence BMD in Japanese male workers.

| S-EPMC3047666 | biostudies-literature

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