ArticleNature communications2021
The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanistic Insights into Redox-Dependent Macropinocytosis in Primary Human Neutrophils.Antioxidants (Basel, Switzerland) · 2026Article
- Toll-like receptor 4 signaling links cytoskeletal remodeling to lipid accumulation in macrophages.Inflammation and regeneration · 2026Review
- Non-decameric NLRP3 reveals a TGN/MTOC-distal pathway of inflammasome activation.Nature communications · 2026Article
- PIKfyve is required for efficient phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes.Journal of cell science · 2026Article
- Article
- Synthetic aptamer mechanoreceptors enable cell-specific force sensing and temporal control via DNA circuits.Nature communications · 2026Article
- Macropinocytosis and Vascularization Determine Response to mTOR Inhibitors in Lung Squamous Cell Carcinoma.Cancer research · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Loss of Fanconi anemia proteins causes a reliance on lysosomal exocytosis.Cell death & disease · 2025Article
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome formation.The Journal of cell biology · 2024Article
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- The role of Phafin proteins in cell signaling pathways and diseases.Open life sciences · 2024Review
- Contrasting effects of filamin A and B proteins in modulating filovirus entry.PLoS pathogens · 2023Article
- Phafins Are More Than Phosphoinositide-Binding Proteins.International journal of molecular sciences · 2023Review
- CYRI proteins: controllers of actin dynamics in the cellular 'eat vs walk' decision.Biochemical Society transactions · 2023Review
- Phosphoinositides as membrane organizers.Nature reviews. Molecular cell biology · 2022Review
- A pH-Driven Small-Molecule Nanotransformer Hijacks Lysosomes and Overcomes Autophagy-Induced Resistance in Cancer.Angewandte Chemie (International ed. in English) · 2022Article
- The PH Domain and C-Terminal polyD Motif of Phafin2 Exhibit a Unique Concurrence in Animals.Membranes · 2022Article
- The Role and Therapeutic Potential of Macropinocytosis in Cancer.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uptake of large volumes of extracellular fluid by actin-dependent macropinocytosis has an important role in infection, immunity and cancer development. A key question is how actin assembly and disassembly are coordinated around macropinosomes to allow them to form and subsequently pass through the dense actin network underlying the plasma membrane to move towards the cell center for maturation. Here we show that the PH and FYVE domain protein Phafin2 is recruited transiently to newly-formed macropinosomes by a mechanism that involves coincidence detection of PtdIns3P and PtdIns4P. Phafin2 also interacts with actin via its PH domain, and recruitment of Phafin2 coincides with actin reorganization around nascent macropinosomes. Moreover, forced relocalization of Phafin2 to the plasma membrane causes rearrangement of the subcortical actin cytoskeleton. Depletion of Phafin2 inhibits macropinosome internalization and maturation and prevents KRAS-transformed cancer cells from utilizing extracellular protein as an amino acid source. We conclude that Phafin2 promotes macropinocytosis by controlling timely delamination of actin from nascent macropinosomes for their navigation through the dense subcortical actin network.
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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.