ArticleMolecular metabolism2018
The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial triglyceride-rich lipoproteins.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.Nature cancer · 2026Article
- Loss of Early Growth Response Protein 1 in the Liver Leads to Hepatic Lipid Accumulation Driven by an Imbalance Between Fatty Acid β-Oxidation and Oxidative Phosphorylation.Gastro hep advances · 2026Article
- As a New Tumor Suppressor Gene, PID1 Activates the AMPK-mTOR Signal to Inhibit the Progression of Bladder Cancer.Research and reports in urology · 2025Article
- Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease.Cellular and molecular gastroenterology and hepatology · 2025Review
- Dual role of PID1 in regulating apoptosis induced by distinct anticancer-agents through AKT/Raf-1-dependent pathway in hepatocellular carcinoma.Cell death discovery · 2023Article
- RNA-seq reveals insights into molecular mechanisms of metabolic restoration via tryptophan supplementation in low birth weight piglet model.Journal of animal science · 2022Article
- Transgelin: a new gene involved in LDL endocytosis identified by a genome-wide CRISPR-Cas9 screen.Journal of lipid research · 2022Article
- Function of the endolysosomal network in cholesterol homeostasis and metabolic-associated fatty liver disease (MAFLD).Molecular metabolism · 2021Review
- Apolipoprotein E and Atherosclerosis.Current atherosclerosis reports · 2021Review
- Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice.Journal of lipid research · 2020Article
- Metabolic regulation through the endosomal system.Traffic (Copenhagen, Denmark) · 2019Review
- PID1 regulates insulin-dependent glucose uptake by controlling intracellular sorting of GLUT4-storage vesicles.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins.Frontiers in endocrinology · 2018Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInsulin resistance is associated with impaired receptor dependent hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL) receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by insulin action contributes to the rapid clearance of TRL in the postprandial state. Here, we investigated the hypothesis that the adaptor protein phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1 function, thereby controlling hepatic endocytosis of postprandial lipoproteins.
methodsLocalization and interaction of PID1 and LRP1 in cultured hepatocytes was studied by confocal microscopy of fluorescent tagged proteins, by indirect immunohistochemistry of endogenous proteins, by GST-based pull down and by immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr-deficient (Ldlr
resultsPID1 co-localized in perinuclear endosomes and was found associated with LRP1 under fasting conditions. We identified the distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the site critical for the interaction with PID1. Insulin-mediated NPxY-phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1 translocation to the plasma membrane. PID1 deletion resulted in higher LRP1 abundance at the cell surface, higher LDLR protein levels and, paradoxically, reduced total LRP1. The latter can be explained by higher receptor shedding, which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1 deficiency alone led to increased LDLR-dependent endocytosis of postprandial lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion on an Ldlr
conclusionsBy acting as an insulin-dependent retention adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of postprandial lipoproteins. PID1 inhibition provides a novel approach to lower plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function of both LRP1 and LDLR in the liver.
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