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🚨 Lipid Time! 🚨 Excited to share our latest story now on @biorxiv-biochem.bsky.social ! Our brilliant PhD student @manpreet0700.bsky.social , together with @walter-nickel-bzh.bsky.social and myself, shows how PI(4,5)P₂ asymmetry in the plasma membrane drives the unconventional secretion of FGF2! 👇👇👇

FGF2 translocates in 200ms in cells—but takes ~1hr in reconstitution systems. What drives this rapid kinetics in cells? 🏃‍♂️⏩⏩ Many auxiliary factors are missing in reconstituted systems. We pinpoint transbilayer PI(4,5)P₂ asymmetry as a key contributor to efficient membrane translocation.

If our hypothesis holds, disrupting PI(4,5)P₂ asymmetry in cells should slow FGF2 translocation. To test this, @manpreet0700.bsky.social introduced PI(4,5)P₂ micelles in the media—enriching the outer leaflet and disturbing the natural asymmetry. And yes, it made a difference.

To quantify FGF2 translocation kinetics, we developed a new single-cell confocal assay. Following doxycycline induction, we removed surface FGF2-GFP with heparin wash and tracked its rapid reappearance—capturing a fresh wave of secretion at different incubation times

FGF2 secretion depends on PI(4,5)P₂ asymmetry across the plasma membrane. Disrupting this asymmetry with exogenous PI(4,5)P₂ blocks FGF2 translocation—an effect that reverses as cells restore asymmetry over time