ArticleProceedings of the National Academy of Sciences of the United States of America2025
Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Phase separation across membranes and condensates in cell organization and function.Nature reviews. Molecular cell biology · 2026Review
- Shadow-Calibrated Stereo Vision for Colorimetric Sweat Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated microRNA-mRNA network analysis of invasive and immune-inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread.Molecular and clinical oncology · 2026Article
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- Rules railroad: Syntax-inspired diagrams for visualizing and understanding rule-based model specifications.PLoS computational biology · 2026Article
- Lipid-Mediated Assembly of Biomolecular Condensates: Mechanisms, Regulation, and Therapeutic Implications.Biology · 2025Review
- Article
- 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
- Visualizing mechanistic models by integrating site-specific molecular details into reaction networks.Frontiers in molecular biosciences · 2025Article
- Measurement of solubility product reveals the interplay of oligomerization and self-association for defining condensate formation.Molecular biology of the cell · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of chloride ions, dehydration of cell surfaces, and subsequent damage to airway and ductal organs. Beyond its function as a chloride channel, interactions between CFTR, epithelium sodium channel, and solute carrier (SLC) transporter family membrane proteins and cytoplasmic proteins, including calmodulin and Na+/H+ exchanger regulatory factor-1 (NHERF-1), coregulate ion homeostasis. CFTR has also been observed to form mesoscale membrane clusters. However, the contributions of multivalent protein and lipid interactions to cluster formation are not well understood. Using a combination of computational modeling and biochemical reconstitution assays, we demonstrate that multivalent interactions with CFTR protein binding partners, calcium, and membrane cholesterol can induce mesoscale CFTR cluster formation on model membranes. Phosphorylation of the intracellular domains of CFTR also promotes mesoscale cluster formation in the absence of calcium, indicating that multiple mechanisms can contribute to CFTR cluster formation. Our findings reveal that coupling of multivalent protein and lipid interactions promotes CFTR cluster formation consistent with membrane-associated biological phase separation.
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