The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2

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Legrand , C , Saleppico , R , Sticht , J , Lolicato , F , Müller , H-M , Wegehingel , S , Dimou , E , Steringer , J P , Ewers , H , Vattulainen , I , Freund , C & Nickel , W 2020 , ' The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2 ' , Communications Biology , vol. 3 , no. 1 , 141 . https://doi.org/10.1038/s42003-020-0871-y

Title: The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2
Author: Legrand, Cyril; Saleppico, Roberto; Sticht, Jana; Lolicato, Fabio; Müller, Hans-Michael; Wegehingel, Sabine; Dimou, Eleni; Steringer, Julia P.; Ewers, Helge; Vattulainen, Ilpo; Freund, Christian; Nickel, Walter
Contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2020-03-25
Language: eng
Number of pages: 16
Belongs to series: Communications Biology
ISSN: 2399-3642
URI: http://hdl.handle.net/10138/314547
Abstract: 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.
Subject: CELL-SURFACE
ESSENTIAL COMPONENTS
EXPORT MACHINERY
FGF-2
HIV-1 TAT
MECHANISMS
MEMBRANE PORE FORMATION
PLASMA-MEMBRANE
PROTEIN-PROTEIN DOCKING
TRANSLOCATION
1182 Biochemistry, cell and molecular biology
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