ArticleBiophysical journal2010
ADF/cofilin binds phosphoinositides in a multivalent manner to act as a PIP(2)-density sensor.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
- Optogenetic control of PLC-γ1 activity directs cell motility.The Journal of cell biology · 2026Article
- Molecular insights into profilin 1-dependent regulation of cellular phosphatidylinositol (4,5)-bisphosphate.Journal of cell science · 2026Article
- Cardiac mechanotransduction from development to disease.APL bioengineering · 2026Review
- Molecular insights into Profilin1-dependent regulation of cellular phosphatidylinositol-(4,5)-bisphosphate.bioRxiv : the preprint server for biology · 2025Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- Obesity-induced cofilin1 pathway dysregulation: Possible molecular links between neuroinflammation, cognitive decline, and Alzheimer's disease biomarkers.IBRO neuroscience reports · 2025Article
- Optogenetic control of PLC-γ1 activity polarizes cell motility.bioRxiv : the preprint server for biology · 2025Article
- Structure and Functions of Actin and Actin-Binding Proteins inPathogens (Basel, Switzerland) · 2025Review
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- The potassium channel KNature communications · 2025Article
- Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics.Cell death & disease · 2025Review
- Iron triggersmBio · 2025Article
- Regulation and signaling of the LIM domain kinases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Ion channel TRPV2 is critical in enhancing B cell activation and function.The Journal of experimental medicine · 2024Article
- Chemokine Receptor Antagonists Prevent and Reverse Cofilin-Actin Rod Pathology and Protect Synapses in Cultured Rodent and Human iPSC-Derived Neurons.Biomedicines · 2024Article
- Actin Bundles Dynamics and Architecture.Biomolecules · 2023Review
- PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022Article
- Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding.EMBO reports · 2022Article
- The inositol 5-phosphatase INPP5B regulates B cell receptor clustering and signaling.The Journal of cell biology · 2022Article
- Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actin-depolymerizing-factor (ADF)/cofilins have emerged as key regulators of cytoskeletal dynamics in cell motility, morphogenesis, endocytosis, and cytokinesis. The activities of ADF/cofilins are regulated by membrane phospholipid PI(4,5)P(2) in vitro and in cells, but the mechanism of the ADF/cofilin-PI(4,5)P(2) interaction has remained controversial. Recent studies suggested that ADF/cofilins interact with PI(4,5)P(2) through a specific binding pocket, and that this interaction is dependent on pH. Here, we combined systematic mutagenesis with biochemical and spectroscopic methods to elucidate the phosphoinositide-binding mechanism of ADF/cofilins. Our analysis revealed that cofilin does not harbor a specific PI(4,5)P(2)-binding pocket, but instead interacts with PI(4,5)P(2) through a large, positively charged surface of the molecule. Cofilin interacts simultaneously with multiple PI(4,5)P(2) headgroups in a cooperative manner. Consequently, interactions of cofilin with membranes and actin exhibit sharp sensitivity to PI(4,5)P(2) density. Finally, we show that cofilin binding to PI(4,5)P(2) is not sensitive to changes in the pH at physiological salt concentration, although the PI(4,5)P(2)-clustering activity of cofilin is moderately inhibited at elevated pH. Collectively, our data demonstrate that ADF/cofilins bind PI(4,5)P(2) headgroups through a multivalent, cooperative mechanism, and suggest that the actin filament disassembly activity of ADF/cofilin can be accurately regulated by small changes in the PI(4,5)P(2) density at cellular membranes.
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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.