LDLRAP1 Antibody
Description
Biological Context of LDLRAP1
LDLRAP1 is an adaptor protein critical for the internalization of low-density lipoprotein (LDL) receptors in hepatocytes and lymphocytes . It facilitates the removal of cholesterol-rich LDL particles from the bloodstream by stabilizing the interaction between LDL receptors and clathrin-coated pits . Mutations in the LDLRAP1 gene cause autosomal recessive hypercholesterolemia (ARH), characterized by elevated LDL cholesterol levels and premature atherosclerosis .
Role of LDLRAP1 Antibodies
Antibodies targeting LDLRAP1 are used in:
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Immunoblotting and immunohistochemistry to study protein expression in tissues or cells .
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Flow cytometry to assess receptor internalization efficiency in experimental models .
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Diagnostic assays to confirm LDLRAP1 dysfunction in hypercholesterolemic patients .
| Antibody Type | Application | Citation |
|---|---|---|
| Monoclonal (e.g., clone Q5SW96) | Western blot, IHC for ARH diagnosis | |
| Polyclonal | ELISA for serum LDLRAP1 levels | |
| Anti-LDLRAP1 (rabbit) | Mouse atherosclerosis models |
Mechanistic Studies
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Deletion of LDLRAP1 in mice leads to hypercholesterolemia, atherosclerotic plaque formation, and insulin resistance . Antibodies have been used to confirm the absence of LDLRAP1 in knockout models .
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LDLRAP1 antibodies revealed altered adipose tissue metabolism in ARH, linking it to obesity and metabolic syndrome .
Therapeutic Implications
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Targeting LDLRAP1 with monoclonal antibodies could enhance LDL receptor internalization, reducing circulating LDL cholesterol in hypercholesterolemic patients .
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Preclinical studies using LDLRAP1-deficient mice suggest antibodies may help monitor therapeutic interventions aimed at restoring LDL clearance .
Clinical Applications
Antibodies are critical in diagnosing ARH and monitoring treatment efficacy. For example:
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Immunoprecipitation assays using LDLRAP1 antibodies detect protein truncations caused by mutations .
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Serum LDLRAP1 levels, measured via ELISA, correlate with disease severity in ARH patients .
Future Directions
Product Specs
Target Background
LDLRAP1 (also known as ARH) is a clathrin-associated sorting protein (CLASP) that functions as an adapter protein crucial for efficient endocytosis of the low-density lipoprotein receptor (LDLR) in polarized cells like hepatocytes and lymphocytes. Unlike non-polarized cells (fibroblasts), LDLRAP1's role in LDLR endocytosis is essential. While its involvement in LDL binding and internalization is established, its influence on receptor clustering in coated pits remains under investigation. LDLRAP1 likely facilitates LDLR and LDLR-LDL complex endocytosis from coated pits by stabilizing the interaction between the receptor and pit structural components. Furthermore, it may participate in the internalization of other LDLR family members. Its binding to phosphoinositides regulates clathrin bud assembly at the cell surface. Importantly, LDLRAP1 is required for the trafficking of LRP2 to the endocytic recycling compartment, a process necessary for LRP2 proteolysis and subsequent nuclear translocation of a tail fragment that mediates transcriptional repression.
The following studies highlight the significance of LDLRAP1:
- Association of LDLRAP1 with Familial Hypercholesterolemia and Polygenic Hypercholesterolemia in acute coronary syndrome patients aged ≥65 years with LDL-C levels ≥160 mg/dl. PMID: 28958330
- Numb's specific regulation of NPC1L1-mediated cholesterol absorption in human intestine and liver, distinct from ARH and Dab2's selective roles in LDLR-mediated LDL uptake. PMID: 25331956
- Identification and characterization of ARH gene mutations in Autosomal Recessive Hypercholesterolemia patients (Review). PMID: 25225128
- Regulation of lipoprotein internalization by LDLRs in ARH-dependent cells via nitric oxide modulation. PMID: 23564733
- Identification of combined LDL receptor and LDLRAP1 mutations as the cause of severe familial hypercholesterolemia in a Turkish family. PMID: 23510778
- LDLRAP1 (ARH) regulation of ROMK potassium channel endocytosis via a novel variant of the "NPXY" endocytotic signal; LDLRAP1-knockout mice exhibit impaired ROMK physiological regulation. PMID: 19841541
- Crystal structure (1.37-Å resolution) of the ARH phosphotyrosine-binding (PTB) domain complexed with an LDLR tail peptide containing the FxNPxY(0) internalization signal. PMID: 22509010
- LDL receptor/LDLRAP1 double heterozygous mutations and their association with severe xanthomas and atherosclerotic cardiovascular disease in familial hypercholesterolemia. PMID: 21872251
- ARH's involvement in cell cycle progression, potentially through nuclear membrane formation via interaction with lamin B1 or other mitotic proteins; its absence affects cell proliferation and induces premature senescence. PMID: 21778424
- Apical missorting of truncated LDLR (encoding only the FxNPxY motif, LDLR-CT27) in polarized epithelial cells upon ARH knockdown. PMID: 21444685
- Identification of a rare Thr56Met missense mutation in the ARH phosphotyrosine-binding domain; association with hypercholesterolemia resembling familial hypercholesterolemia in 4/1800 Japanese individuals. PMID: 20124734
- Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia. PMID: 19477448
- ARH's function as an adaptor protein coupling LDLR to the endocytic machinery. PMID: 12221107
- Defective sorting adaptor function in ARH patients' hepatocytes leading to faulty LDL receptor traffic and hypercholesterolemia. PMID: 12451172
- Restoration of LDL receptor function in autosomal recessive hypercholesterolemia patient cells via retroviral expression. PMID: 12464675
- Single nucleotide polymorphism (ARH-604C to ARH-604T) changing proline 202 to serine; association with ARH. PMID: 12788851
- ARH's facilitation of megalin endocytosis and escort along its endocytic route. PMID: 14528014
- ARH's requirement for not only LDL.LDLR complex internalization but also efficient LDL receptor binding. PMID: 15166224
- Splice site mutation resulting in a 26-amino acid deletion, losing beta-strands beta6 and beta7 from the PTB domain. PMID: 15599766
- Presence of an AP-2 beta2 appendage-binding sequence in the ARH protein. PMID: 15728179
- ARH's active participation in LDL-LDLR complex internalization, potentially enhancing its packaging into endocytic vesicles. PMID: 16129683
- Exceptionally low Dab2 expression in hepatocytes, possibly explaining the hypercholesterolemia associated with ARH loss. PMID: 16870701
- ARH's potential acceleration of later LDLR endocytosis steps in cooperation with AP-2. PMID: 16984970
- Association of a large deletion in the ARH gene with autosomal recessive hypercholesterolemia. PMID: 17686643
- ARH's association with motor and centrosomal proteins and its involvement in centrosome assembly and cytokinesis. PMID: 18417616
- PCSK9-mediated LDLR degradation's partial independence from ARH function. PMID: 19081568
