Plasma membrane transbilayer asymmetry of PI(4,5)P2 drives unconventional secretion of Fibroblast Growth Factor 2

Manpreet Kaur, Fabio Lolicato () and Walter Nickel ()
Additional contact information
Manpreet Kaur: Heidelberg University Biochemistry Center
Fabio Lolicato: Heidelberg University Biochemistry Center
Walter Nickel: Heidelberg University Biochemistry Center

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Unconventional secretion of Fibroblast Growth Factor 2 (FGF2) is mediated by direct translocation across the plasma membrane. This process is initiated by PI(4,5)P2-dependent FGF2 oligomerization at the inner plasma membrane leaflet. PI(4,5)P2 is a non-bilayer lipid that accumulates at sites of FGF2 oligomerization, imposing severe membrane stress that is relieved by the formation of a lipidic membrane pore. At the outer leaflet, FGF2 oligomers are captured and disassembled by the heparan sulfate proteoglycan Glypican-1 (GPC1), making available FGF2 to engage in ternary signaling complexes on cell surfaces. Using an in vitro reconstitutions system, this study provides direct evidence that transbilayer asymmetry of PI(4,5)P2 promotes rapid kinetics of membrane pore formation. Likewise, FGF2 secretion from cells is inhibited when PI(4,5)P2 plasma membrane transbilayer asymmetry is disrupted. We propose the asymmetric distribution of PI(4,5)P2 to lower the energetic barrier for membrane pore formation, enabling rapid kinetics of FGF2 membrane translocation into the extracellular space.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-66860-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-66860-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-66860-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().