Titel: | Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2 |
VerfasserIn: | Lolicato, Fabio Saleppico, Roberto Griffo, Alessandra Meyer, Annalena Scollo, Federica Pokrandt, Bianca Müller, Hans-Michael Ewers, Helge Hähl, Hendrik Fleury, Jean-Baptiste Seemann, Ralf Hof, Martin Brügger, Britta Jacobs, Karin Vattulainen, Ilpo Nickel, Walter |
Sprache: | Englisch |
Titel: | The Journal of Cell Biology |
Bandnummer: | 221 |
Heft: | 11 |
Verlag/Plattform: | Rockefeller University Press |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | Biochemistry Biophysics Membrane and lipid biology Trafficking |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
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. |
DOI der Erstveröffentlichung: | 10.1083/jcb.202106123 |
URL der Erstveröffentlichung: | https://doi.org/10.1083/jcb.202106123 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-389152 hdl:20.500.11880/35107 http://dx.doi.org/10.22028/D291-38915 |
ISSN: | 1540-8140 0021-9525 |
Datum des Eintrags: | 6-Feb-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplemental material |
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Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Physik |
Professur: | NT - Prof. Dr. Karin Jacobs NT - Prof. Dr. Ralf Seemann |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes
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