The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2
Copyright policy )The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2
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.
- Freie Universität Berlin Germany
- Tampere University Finland
- Heidelberg University Germany
- University of Helsinki Finland
Phosphatidylinositol 4,5-Diphosphate, 570, ESSENTIAL COMPONENTS, 572, FGF-2, CHO Cells, Molecular Dynamics Simulation, 114 Physical sciences, Second Messenger Systems, Article, 114, MECHANISMS, Cricetulus, CELL-SURFACE, Animals, MEMBRANE PORE FORMATION, Protein Interaction Domains and Motifs, HIV-1 TAT, Biochemistry, cell and molecular biology, Secretory Pathway, Cell Membrane, TRANSLOCATION, Molecular Docking Simulation, EXPORT MACHINERY, Protein Transport, PLASMA-MEMBRANE, PROTEIN-PROTEIN DOCKING, Fibroblast Growth Factor 2, Sodium-Potassium-Exchanging ATPase, Protein Binding
Phosphatidylinositol 4,5-Diphosphate, 570, ESSENTIAL COMPONENTS, 572, FGF-2, CHO Cells, Molecular Dynamics Simulation, 114 Physical sciences, Second Messenger Systems, Article, 114, MECHANISMS, Cricetulus, CELL-SURFACE, Animals, MEMBRANE PORE FORMATION, Protein Interaction Domains and Motifs, HIV-1 TAT, Biochemistry, cell and molecular biology, Secretory Pathway, Cell Membrane, TRANSLOCATION, Molecular Docking Simulation, EXPORT MACHINERY, Protein Transport, PLASMA-MEMBRANE, PROTEIN-PROTEIN DOCKING, Fibroblast Growth Factor 2, Sodium-Potassium-Exchanging ATPase, Protein Binding
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