The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2
FGF2 is a tumor cell survival factor that is exported from cells by an ER/Golgi-independent secretory pathway. This unconventional mechanism of protein secretion is based on direct translocation of FGF2 across the plasma membrane. The Na,K-ATPase has previously been shown to play a role in this proc...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
25 March 2020
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| In: |
Communications biology
Year: 2020, Jahrgang: 3 |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-020-0871-y |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s42003-020-0871-y Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s42003-020-0871-y 
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| Verfasserangaben: | Cyril Legrand, Roberto Saleppico, Jana Sticht, Fabio Lolicato, Hans-Michael Müller, Sabine Wegehingel, Eleni Dimou, Julia P. Steringer, Helge Ewers, Ilpo Vattulainen, Christian Freund & Walter Nickel |
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| 245 | 1 | 4 | |a The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2 |c Cyril Legrand, Roberto Saleppico, Jana Sticht, Fabio Lolicato, Hans-Michael Müller, Sabine Wegehingel, Eleni Dimou, Julia P. Steringer, Helge Ewers, Ilpo Vattulainen, Christian Freund & Walter Nickel |
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| 520 | |a FGF2 is a tumor cell survival factor that is exported from cells by an ER/Golgi-independent secretory pathway. This unconventional mechanism of protein secretion is based on direct translocation of FGF2 across the plasma membrane. The Na,K-ATPase has previously been shown to play a role in this process, however, the underlying mechanism has remained elusive. Here, we define structural elements that are critical for a direct physical interaction between FGF2 and the α1 subunit of the Na,K-ATPase. In intact cells, corresponding FGF2 mutant forms were impaired regarding both recruitment at the inner plasma membrane leaflet and secretion. Ouabain, a drug that inhibits both the Na,K-ATPase and FGF2 secretion, was found to impair the interaction of FGF2 with the Na,K-ATPase in cells. Our findings reveal the Na,K-ATPase as the initial recruitment factor for FGF2 at the inner plasma membrane leaflet being required for efficient membrane translocation of FGF2 to cell surfaces. | ||
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