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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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Main Authors: Legrand, Cyril (Author) , Saleppico, Roberto (Author) , Sticht, Jana (Author) , Lolicato, Fabio (Author) , Müller, Hans-Michael (Author) , Wegehingel, Sabine (Author) , Dimou, Eleni (Author) , Steringer, Julia P. (Author) , Ewers, Helge (Author) , Vattulainen, Ilpo (Author) , Freund, Christian (Author) , Nickel, Walter (Author)
Format: Article (Journal)
Language:English
Published: 25 March 2020
In: Communications biology
Year: 2020, Volume: 3
ISSN:2399-3642
DOI:10.1038/s42003-020-0871-y
Online Access: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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Author Notes: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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Summary: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.
Item Description:Im Titel ist die Ziffer 2 bei "PI(4,5)P2" tiefgestellt
Gesehen am 10.08.2020
Physical Description:Online Resource
ISSN:2399-3642
DOI:10.1038/s42003-020-0871-y

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