Evidence map›Paper›PMID 12925709›Full record

ArticleThe Journal of cell biology2003

ARF6 regulates a plasma membrane pool of phosphatidylinositol(4,5)bisphosphate required for regulated exocytosis.

Yoshikatsu Aikawa, Thomas F J Martin

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

106 citing papers in PubMed, 228 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025
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  5. Iron triggersmBio · 2025
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  7. The Silencing ofInternational journal of molecular sciences · 2024
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  8. Identification and Analysis of the Expression of theInternational journal of molecular sciences · 2023
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  9. Article
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  11. The Arf family GTPases: Regulation of vesicle biogenesis and beyond.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Physiological and Pathological Roles of the Cytohesin Family in Neurons.International journal of molecular sciences · 2022
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

46 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Yoshikatsu AikawaDepartment of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Thomas F J Martin
University of Wisconsin–Madison · US

Funding

THE MECHANISM OF ACTION OF THYROTROPIN-RELEASING HORMONER01DK025861 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1986 to 2024
$5.6M
THE MECHANISM OF ACTION OF THYROTROPIN-RELEASING HORMONER37DK025861 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1991 to 2008
$3.3M
NIDDK NIH HHS DK 25861NIDDK NIH HHS R01 DK025861NIDDK NIH HHS R37 DK025861
6 · The paper itself

Abstract

ADP-ribosylation factor (ARF) 6 regulates endosomal plasma membrane trafficking in many cell types, but is also suggested to play a role in Ca2+-dependent dense-core vesicle (DCV) exocytosis in neuroendocrine cells. In the present work, expression of the constitutively active GTPase-defective ARF6Q67L mutant in PC12 cells was found to inhibit Ca2+-dependent DCV exocytosis. The inhibition of exocytosis was accompanied by accumulation of ARFQ67L, phosphatidylinositol 4,5-bisphosphate (PIP2), and the phosphatidylinositol 4-phosphate 5-kinase type I (PIP5KI) on endosomal membranes with their corresponding depletion from the plasma membrane. That the depletion of PIP2 and PIP5K from the plasma membrane caused the inhibition of DCV exocytosis was demonstrated directly in permeable cell reconstitution studies in which overexpression or addition of PIP5KIgamma restored Ca2+-dependent exocytosis. The restoration of exocytosis in ARF6Q67L-expressing permeable cells unexpectedly exhibited a Ca2+ dependence, which was attributed to the dephosphorylation and activation of PIP5K. Increased Ca2+ and dephosphorylation stimulated the association of PIP5KIgamma with ARF6. The results reveal a mechanism by which Ca2+ influx promotes increased ARF6-dependent synthesis of PIP2. We conclude that ARF6 plays a role in Ca2+-dependent DCV exocytosis by regulating the activity of PIP5K for the synthesis of an essential plasma membrane pool of PIP2.

Indexed as

ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsCalciumCell MembraneEndosomesExocytosisPC12 CellsPhosphatidylinositol 4,5-DiphosphatePhosphorylationrab11 GTP-Binding Proteinsrab GTP-Binding ProteinsRatsTransferrinADP-Ribosylation Factor 6ADP-Ribosylation FactorsArf6 protein, ratCalciumPhosphatidylinositol 4,5-Diphosphaterab11 GTP-Binding Proteinsrab GTP-Binding ProteinsTransferrin

Identifiers

PMID12925709
PMCPMC2173784
OpenAlexW2031057786

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.