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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
In Beziehung stehendes Objekt: https://cdn.rupress.org/rup/content_public/journal/jcb/221/11/10.1083_jcb.202106123/1/jcb_202106123_tables1.docx?Expires=1678693977&Signature=NfX00DFwUoRc8fceXiqUK4AbmrGwtf3eUUyfedtLbnukqtbfTZlYdMOBlFbwrqZY98ucQTSJjOsCp8GnYLRVx7frbQenXGcGSPUtx4cAQYldTQebyeJQEiYEw5UKOTNK0LRzcBR5m6UxCNKApIJDziW6LSSE~9pIV0fdcQzYBQOV4gJv9wDZS5ZykQftM8tc3aXnbno4q10678~o-Epptixr9rQT7OX5X7M81T9xndBG~yH20jeBWOH1VLX1j63Jn-W0YmwZ00suUaUVCE6DlwXdbSf1SVq-2t~C~~gV6wzobYi2Aw1aa16vHPIR2pOMiDv-5KTsRwr5BfjF2LAvjg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
https://cdn.rupress.org/rup/content_public/journal/jcb/221/11/10.1083_jcb.202106123/1/jcb_202106123_tables2.docx?Expires=1678693977&Signature=UVfZn6Okd0rlH4WxMnANCEpAcBfkvQCvufEnaRhCkXj5gliEwRvN69txq1gIHTJ9UrQBT9s5YGjloSbB5bYIM-jWGEtv9O6FcWlc49RrIbwzXz5WvpwPu6ksvDBaRMPxD~l3U4Hy06szKx30lADniT09B2pvWOTbq5H9bjwr7~bC8nEauBYZE3S8h0WdgZq9wHHsUguVdf40kri~JjbRnAZsAeVmKsdTPUWJeNIlXma0Cb0qaGU5whtqz0FRe82raSVSa1761HCQRggEIZIerRigpaHhj06kDxPXjn8P~tn9uoB~9m0FV4C-sslqI1kPEN9684RgsO5wOMZ97PYpag__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
https://cdn.rupress.org/rup/content_public/journal/jcb/221/11/10.1083_jcb.202106123/1/jcb_202106123_tables3.docx?Expires=1678693977&Signature=eZX11iyfW8MswFGNgi5v4iCRTMGdf~vVtFV30sHhJXpgSLEPf9vbyq6w4MLeSANLq35bEOd~YtZR1b1h8ulVh2YeIm9qjhsmzeujZZRBUoyQNLxSi5nt60ND2iobZtFOHI3I3mCRuXqLOs2wLXCp5FdzvqthF37-WZDHYxL85VGPBuxIQoeaWM6A8rU50wSEuml2tCwzg75jRZ0D~U6WGmOrkUJ8Q3P37R26W7nNihjdTiSarAx8aKSRtfJdhOruVAHmlvWGgj9s6ngfHHa3mAKJTEGAs6Upu7uGX-kvbLxCNmUhuQWaZuZHx8UugCGY8DEtlitNgj3kSm8yQWBbKA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
https://cdn.rupress.org/rup/content_public/journal/jcb/221/11/10.1083_jcb.202106123/1/jcb_202106123_sourcedatafs4.pdf?Expires=1678693978&Signature=sIFbzDxpGjyVpE3bC1RlbR2zOR83KM3TH9q26pS-oi-juvoampTYUk6KZQny7jmXNma~HLHLVEdnaWk~So6CBiPkrCEnjmYmNDnM1iCDQOCNxDcjEsHcY3xpjbuNHa938Sssk6a0OENAVscb3rykoHnxbiD6NhGjG08EfhWt1BJe~bb2qUMOaMBckCipQRWgIp-IOWvRbtPi1-rVhnU8MsMdk5uJGGWz1yOcH2SdyITIpL3MI~bD0~qVivW6pttCWEF9yZW4l2ua2naVIK9uRd7hykn4hzvkSV9kOEZIZgy6n9doa3rt0klfZoJE02JR7kndR8SBD~~l~w-cbL2aNA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
https://cdn.rupress.org/rup/content_public/journal/jcb/221/11/10.1083_jcb.202106123/1/jcb_202106123_sourcedatafs5.pdf?Expires=1678693978&Signature=j4So0P0UTJ7As5A5ljzdi2-UcxZNjeWeMEcxrzOaMGKyL2a1ydprvyKtTN8-0zTWEr40MVTJnOtgcUoOefoYJHzjMDmWpkjzjvOx-~xJ-l6mXN7G2LyUtgOdpIqS1W2hIPPa0XykEdlLTjbPpc0yYJ3iYwSfLo8bCve7G0-FEFaHlvwsL-URFLrzaLNd7ZLUn96R3B94EgnwVD31PS98r8DZUoKfE57ZGYRXsLLq-rYAS~PVqlBDTnXIZvLh3hwbP2eVWG~8ygEqkMCm8E6q5QzbBB9lm8I9315REFis8qom5MJXkNDJLgyrxCRW9PU-vm3PtvSb9lwPrScTeYMmcQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
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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