Evidence map›Paper›PMID 25533462›Full record

ArticleThe Journal of biological chemistry2015

A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2.

Sonja Zacherl, Giuseppe La Venuta, Hans-Michael Müller, Sabine Wegehingel, Eleni Dimou, Peter Sehr, Joe D Lewis, Holger Erfle, Rainer Pepperkok, Walter Nickel

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Glycolytic activation of β-cell NaMolecular metabolism · 2026
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  5. Conventional and Unconventional Protein Secretion in Yeast and Animal Cells.Methods in molecular biology (Clifton, N.J.) · 2024
    Review
  6. Article
  7. Role of PI(4,5)P2 and Cholesterol in Unconventional Protein Secretion.Advances in experimental medicine and biology · 2023
    Article
  8. Article
  9. Review
  10. Article
  11. Unconventional Secretion, Gate to Homeoprotein Intercellular Transfer.Frontiers in cell and developmental biology · 2022
    Review
  12. Review
  13. Article
  14. Article
  15. The Cell Biology of Tau Secretion.Frontiers in molecular neuroscience · 2020
    Review
  16. Article
  17. Article
  18. Tau Secretion: Good and Bad for Neurons.Frontiers in neuroscience · 2019
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Sonja ZacherlFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Giuseppe La VenutaFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Hans-Michael MüllerFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Sabine WegehingelFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Eleni DimouFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Peter Sehrthe European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany, and.
Joe D Lewisthe European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany, and.
Holger ErfleBioQuant, Heidelberg University, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
Rainer Pepperkokthe European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany, and.
Walter NickelFrom the Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany, walter.nickel@bzh.uni-heidelberg.de.
European Bioinformatics Institute · GBHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Secretory PathwayFibroblast Growth Factor 2HeLa CellsHumansProtein BindingProtein Structure, TertiarySodium-Potassium-Exchanging ATPaseATP1A1 protein, humanATP1B1 protein, humanATP1B3 protein, humanFibroblast Growth Factor 2Sodium-Potassium-Exchanging ATPaseATP1A1Fibroblast Growth Factor (FGF)Heparan SulfateMembrane RecruitmentMembrane TranslocationNa+/K+-ATPasePhosphoinositidePlasma MembraneTec KinaseUnconventional Secretion

Identifiers

PMID25533462
PMCPMC4319031
OpenAlexW2082031266

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.