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| Verfasst von: | Lolicato, Fabio [VerfasserIn]  |
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| | Saleppico, Roberto [VerfasserIn] |
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| | Griffo, Alessandra [VerfasserIn] |
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| | Meyer, Annalena [VerfasserIn] |
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| | Scollo, Federica [VerfasserIn] |
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| | Pokrandt, Bianca [VerfasserIn] |
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| | Müller, Hans-Michael [VerfasserIn] |
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| | Ewers, Helge [VerfasserIn] |
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| | Hähl, Hendrik [VerfasserIn] |
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| | Fleury, Jean-Baptiste [VerfasserIn] |
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| | Seemann, Ralf [VerfasserIn] |
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| | Hof, Martin [VerfasserIn] |
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| | Brügger, Britta [VerfasserIn] |
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| | Jacobs, Karin [VerfasserIn] |
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| | Vattulainen, Ilpo [VerfasserIn] |
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| | Nickel, Walter [VerfasserIn] |
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| Titel: | Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2 |
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| Verf.angabe: | Fabio Lolicato, Roberto Saleppico, Alessandra Griffo, Annalena Meyer, Federica Scollo, Bianca Pokrandt, Hans-Michael Müller, Helge Ewers, Hendrik Hähl, Jean-Baptiste Fleury, Ralf Seemann, Martin Hof, Britta Brügger, Karin Jacobs, Ilpo Vattulainen, and Walter Nickel |
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| E-Jahr: | 2022 |
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| Jahr: | September 29 2022 |
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| Umfang: | 29 S. |
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| Fussnoten: | Im Titel ist die Zahl 2 im Ausdruck "PI(4,5)P2" tiefgestellt ; Gesehen am 21.03.2023 |
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| Titel Quelle: | Enthalten in: The journal of cell biology |
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| Ort Quelle: | New York, NY : Rockefeller Univ. Press, 1962 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 221(2022), 11 vom: Sept., Artikel-ID e202106123, Seite 1-29 |
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| ISSN Quelle: | 1540-8140 |
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| 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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| DOI: | doi:10.1083/jcb.202106123 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1083/jcb.202106123 |
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| | DOI: https://doi.org/10.1083/jcb.202106123 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1839685506 |
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| Verknüpfungen: | → Zeitschrift |
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Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2 / Lolicato, Fabio [VerfasserIn]; September 29 2022 (Online-Ressource)
