A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2
Previous studies proposed a role for the Na/K-ATPase in unconventional secretion of fibroblast growth factor 2 (FGF2). This conclusion was based upon pharmacological inhibition of FGF2 secretion in the presence of ouabain. However, neither independent experimental evidence nor a potential mechanism...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2015
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| In: |
The journal of biological chemistry
Year: 2014, Jahrgang: 290, Heft: 6, Pages: 3654-3665 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.590067 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M114.590067 Verlag, lizenzpflichtig, Volltext: http://www.jbc.org/content/290/6/3654 
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| Verfasserangaben: | Sonja Zacherl, Giuseppe La Venuta, Hans-Michael Müller, Sabine Wegehingel, Eleni Dimou, Peter Sehr, Joe D. Lewis, Holger Erfle, Rainer Pepperkok, and Walter Nickel |
| Zusammenfassung: | Previous studies proposed a role for the Na/K-ATPase in unconventional secretion of fibroblast growth factor 2 (FGF2). This conclusion was based upon pharmacological inhibition of FGF2 secretion in the presence of ouabain. However, neither independent experimental evidence nor a potential mechanism was provided. Based upon an unbiased RNAi screen, we now report the identification of ATP1A1, the α1-chain of the Na/K-ATPase, as a factor required for efficient secretion of FGF2. As opposed to ATP1A1, down-regulation of the β1- and β3-chains (ATP1B1 and ATP1B3) of the Na/K-ATPase did not affect FGF2 secretion, suggesting that they are dispensable for this process. These findings indicate that it is not the membrane potential-generating function of the Na/K-ATPase complex but rather a so far unidentified role of potentially unassembled α1-chains that is critical for unconventional secretion of FGF2. Consistently, in the absence of β-chains, we found a direct interaction between the cytoplasmic domain of ATP1A1 and FGF2 with submicromolar affinity. Based upon these observations, we propose that ATP1A1 is a recruitment factor for FGF2 at the inner leaflet of plasma membranes that may control phosphatidylinositol 4,5-bisphosphate-dependent membrane translocation as part of the unconventional secretory pathway of FGF2. |
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| Beschreibung: | Gesehen am 16.07.2020 published online December 22, 2014 |
| Beschreibung: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.590067 |