ArticleThe Journal of biological chemistry2015
Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Effects of Statin Therapy on Plasma Proprotein Convertase Subtilisin/kexin Type 9 and Sortilin Levels in Statin-Naive Patients with Coronary Artery Disease.Journal of atherosclerosis and thrombosis · 2016Trial
- High levels of serum cholesterol increase the risk of developing vessel co-opting tumors in colorectal cancer liver metastases.The FEBS journal · 2026Article
- Molecular recognition of thyroglobulin by sortilin.Nature communications · 2026Article
- Dapagliflozin alleviates mitochondrial damage in the myocardium under diabetic conditions by targeting sortilin.Cellular and molecular life sciences : CMLS · 2025Article
- Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins.EMBO reports · 2024Article
- Induced alternative splicing an opportunity to study PCSK9 protein isoforms at physiologically relevant concentrations.Scientific reports · 2023Article
- Review
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- PCSK9 deficiency alters brain lipid composition without affecting brain development and function.Frontiers in molecular neuroscience · 2022Article
- ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling.Journal of cell science · 2021Article
- Dynamin-related protein 1 inhibition reduces hepatic PCSK9 secretion.Cardiovascular research · 2021Article
- Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications.Frontiers in cardiovascular medicine · 2021Review
- Ser-Phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C (Family With Sequence Similarity 20, Member C) Kinase Enhances Its Ability to Degrade the LDLR (Low-Density Lipoprotein Receptor).Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies.Cardiovascular research · 2019Review
- Hepatocyte sortilin 1 knockout and treatment with a sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice.Journal of lipid research · 2019Article
- Article
- Development of a Cell-Based Assay to Assess Binding of the proNGF Prodomain to Sortilin.Cellular and molecular neurobiology · 2018Article
- APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Article
- Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease.Basic research in cardiology · 2017Review
- Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.FEBS letters · 2017Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Amyloid precursor-like protein 2 (APLP2) and sortilin were reported to individually bind the proprotein convertase subtilisin/kexin type 9 (PCSK9) and regulate its activity on the low-density lipoprotein receptor (LDLR). The data presented herein demonstrate that mRNA knockdowns of APLP2, sortilin, or both in the human hepatocyte cell lines HepG2 and Huh7 do not affect the ability of extracellular PCSK9 to enhance the degradation of the LDLR. Furthermore, mice deficient in APLP2 or sortilin do not exhibit significant changes in liver LDLR or plasma total cholesterol levels. Moreover, cellular overexpression of one or both proteins does not alter PCSK9 secretion, or its activity on the LDLR. We conclude that PCSK9 enhances the degradation of the LDLR independently of either APLP2 or sortilin both ex vivo and in mice. Interestingly, when co-expressed with PCSK9, both APLP2 and sortilin were targeted for lysosomal degradation. Using chemiluminescence proximity and co-immunoprecipitation assays, as well as biosynthetic analysis, we discovered that sortilin binds and stabilizes APLP2, and hence could regulate its intracellular functions on other targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.