ArticleNature communications2012
Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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Who cites it
95 citing papers in PubMed, 171 citations in OpenAlex.
- The planar cell polarity protein Vangl2 interacts with the PDZ-domains of Scribble but not with a unique PDZ-like domain in Inturned.FEBS letters · 2026Article
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells.Science advances · 2026Article
- Intracellular cholesterol: new functions and therapeutic approaches in NSCLC EGFR-TKI resistance.Lipids in health and disease · 2025Review
- Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer.Oncotarget · 2025Article
- Comprehensive in silico characterization of nonsynonymous SNPs in the human ezrin (EZR) gene and their role in disease pathogenesis.Biochemistry and biophysics reports · 2025Article
- Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.Nature structural & molecular biology · 2025Article
- ABCG8‑mediated sterol efflux increases cancer cell progression via the LRP6/Wnt/β‑catenin signaling pathway in radiotherapy‑resistant MDA‑MB‑231 triple‑negative breast cancer cells.International journal of molecular medicine · 2025Article
- Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modulation of the human GlyT1 by clinical drugs and cholesterol.Nature communications · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- Loss of Sc5d results in micrognathia due to a failure in osteoblast differentiation.Journal of advanced research · 2024Article
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- St. John's wort extract Ze 117 alters the membrane fluidity of C6 glioma cells by influencing cellular cholesterol metabolism.Scientific reports · 2024Article
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Regulatory role of cholesterol in modulating actin dynamics and cell adhesive interactions in the trabecular meshwork.bioRxiv : the preprint server for biology · 2024Article
- Cholesterol regulation of mechanosensitive ion channels.Frontiers in cell and developmental biology · 2024Review
- Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape.Signal transduction and targeted therapy · 2023Article
- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Molecules (Basel, Switzerland) · 2023Review
- Cross-talk between CFTR and sphingolipids in cystic fibrosis.FEBS open bio · 2023Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Cholesterol is known to modulate the physical properties of cell membranes, but its direct involvement in cellular signaling has not been thoroughly investigated. Here we show that cholesterol specifically binds many PDZ domains found in scaffold proteins, including the N-terminal PDZ domain of NHERF1/EBP50. This modular domain has a cholesterol-binding site topologically distinct from its canonical protein-binding site and serves as a dual-specificity domain that bridges the membrane and juxta-membrane signaling complexes. Disruption of the cholesterol-binding activity of NHERF1 largely abrogates its dynamic co-localization with and activation of cystic fibrosis transmembrane conductance regulator, one of its binding partners in the plasma membrane of mammalian cells. At least seven more PDZ domains from other scaffold proteins also bind cholesterol and have cholesterol-binding sites, suggesting that cholesterol modulates cell signaling through direct interactions with these scaffold proteins. This mechanism may provide an alternative explanation for the formation of signaling platforms in cholesterol-rich membrane domains.
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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.