ArticleCirculation research2016
PI(4,5)P2 Is Translocated by ABCA1 to the Cell Surface Where It Mediates Apolipoprotein A1 Binding and Nascent HDL Assembly.
Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- ABCA1-Mediated Structural Diversity of HDL Subspecies and Their Proposed Roles in Cardioprotection.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Phosphoinositide flipping governs neomycin sensitivity.Nature cell biology · 2025Article
- The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification.iScience · 2025Article
- ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of Lipids in Atherosclerosis: Focus on Molecular Biology Mechanisms and Therapeutic Approaches.Current medicinal chemistry · 2025Review
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- The Role of ATP-Binding Cassette Proteins in Stem Cell Pluripotency.Biomedicines · 2023Review
- Is reverse cholesterol transport regulated by active cholesterol?Journal of lipid research · 2023Review
- Activity and Structural Dynamics of Human ABCA1 in a Lipid Membrane.Journal of molecular biology · 2023Article
- Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging.Membranes · 2023Review
- Article
- Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis.Advances in experimental medicine and biology · 2023Article
- Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Molecular mechanisms for ABCA1-mediated cholesterol efflux.Cell cycle (Georgetown, Tex.) · 2022Review
- Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.Frontiers in cell and developmental biology · 2022Review
- Structures and Dynamics of Native-State Transmembrane Protein Targets and Bound Lipids.Membranes · 2021Review
- Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2021Review
- CLIC1 recruits PIP5K1A/C to induce cell-matrix adhesions for tumor metastasis.The Journal of clinical investigation · 2021Article
- Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis.Frontiers in cell and developmental biology · 2021Article
- The phosphatidylethanolamine-binding protein DTH1 mediates degradation of lipid droplets inProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 3 countries.
Funding
Abstract
rationaleThe molecular mechanism by which ATP-binding cassette transporter A1 (ABCA1) mediates cellular binding of apolipoprotein A-I (apoA1) and nascent high-density lipoprotein (HDL) assembly is not well understood.
objectiveTo determine the cell surface lipid that mediates apoA1 binding to ABCA1-expressing cells and the role it plays in nascent HDL assembly. METHODS AND
resultsUsing multiple biochemical and biophysical methods, we found that apoA1 binds specifically to phosphatidylinositol (4,5) bis-phosphate (PIP2). Flow cytometry and PIP2 reporter-binding assays demonstrated that ABCA1 led to PIP2 redistribution from the inner to the outer leaflet of the plasma membrane. Enzymatic cleavage of cell surface PIP2 or decreased cellular PIP2 by knockdown of phosphatidylinositol-5-phosphate 4-kinase impaired apoA1 binding and cholesterol efflux to apoA1. PIP2 also increased the spontaneous solubilization of phospholipid liposomes by apoA1. Using site-directed mutagenesis, we found that ABCA1's PIP2 and phosphatidylserine translocase activities are independent from each other. Furthermore, we discovered that PIP2 is effluxed from cells to apoA1, where it is associated with HDL in plasma, and that PIP2 on HDL is taken up by target cells in a scavenger receptor-BI-dependent manner. Mouse plasma PIP2 levels are apoA1 gene dosage-dependent and are >1 μM in apoA1 transgenic mice.
conclusionsABCA1 has PIP2 floppase activity, which increases cell surface PIP2 levels that mediate apoA1 binding and lipid efflux during nascent HDL assembly. We found that PIP2 itself is effluxed to apoA1 and it circulates on plasma HDL, where it can be taken up via the HDL receptor scavenger receptor-BI.
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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.