ArticleThe Journal of cell biology2022
Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- The ER-Golgi intermediate compartment: a central hub integrating membrane trafficking and stress responses.EMBO reports · 2026Review
- Two-dimensional HRS condensates drive the assembly of flat clathrin lattices on endosomes.Nature communications · 2026Article
- Characterization of phospholipid-cholesterol bilayers as self-assembled amphiphile block polymers that contain headgroups.Physica A · 2026Article
- Phosphatidylserine transporters ORP5 and ORP8 control cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.Journal of lipid research · 2026Article
- Unconventional Protein Transport Across the Golgi Ribbon.Sub-cellular biochemistry · 2026Review
- Plasma membrane transbilayer asymmetry of PI(4,5)PNature communications · 2025Article
- Mechanochemical waves in focal adhesions during cell migration.Science advances · 2025Article
- The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.The Journal of cell biology · 2025Article
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Mechanics of biomimetic free-standing lipid membranes: insights into the elasticity of complex lipid compositions.RSC advances · 2024Article
- Phosphoinositide switches in cell physiology - From molecular mechanisms to disease.The Journal of biological chemistry · 2024Review
- Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space.eLife · 2024Article
- A Role for Liquid-Ordered Plasma Membrane Nanodomains Coordinating the Unconventional Secretory Pathway of Fibroblast Growth Factor 2?Frontiers in cell and developmental biology · 2022Review
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
FGF2 is a cell survival factor involved in tumor-induced angiogenesis that is secreted through an unconventional secretory pathway based upon direct protein translocation across the plasma membrane. Here, we demonstrate that both PI(4,5)P2-dependent FGF2 recruitment at the inner plasma membrane leaflet and FGF2 membrane translocation into the extracellular space are positively modulated by cholesterol in living cells. We further revealed cholesterol to enhance FGF2 binding to PI(4,5)P2-containing lipid bilayers. Based on extensive atomistic molecular dynamics (MD) simulations and membrane tension experiments, we proposed cholesterol to modulate FGF2 binding to PI(4,5)P2 by (i) increasing head group visibility of PI(4,5)P2 on the membrane surface, (ii) increasing avidity by cholesterol-induced clustering of PI(4,5)P2 molecules triggering FGF2 oligomerization, and (iii) increasing membrane tension facilitating the formation of lipidic membrane pores. Our findings have general implications for phosphoinositide-dependent protein recruitment to membranes and explain the highly selective targeting of FGF2 toward the plasma membrane, the subcellular site of FGF2 membrane translocation during unconventional secretion of FGF2.
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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.