Evidence map›Paper›PMID 19741095›Full record

ArticleMolecular biology of the cell2009

Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering.

Shirley Leyman, Mazen Sidani, Laila Ritsma, Davy Waterschoot, Robert Eddy, Daisy Dewitte, Olivier Debeir, Christine Decaestecker, Joël Vandekerckhove, Jacco van Rheenen and 3 more

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review of PIP2 in Cellular Signaling, Functions and Diseases.International journal of molecular sciences · 2020
    Review
  2. Review
  3. Article
  4. Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  5. Review
  6. Functions of cofilin in cell locomotion and invasion.Nature reviews. Molecular cell biology · 2013
    Review
  7. Phosphatidylinositol 4,5-bisphosphate: targeted production and signaling.BioEssays : news and reviews in molecular, cellular and developmental biology · 2013
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
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

13 authors at 4 institutions in 3 countries.

Shirley LeymanDepartment of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
Mazen Sidani
Laila Ritsma
Davy Waterschoot
Robert Eddy
Daisy Dewitte
Olivier Debeir
Christine Decaestecker
Joël Vandekerckhove
Jacco van Rheenen
Christophe Ampe
John Condeelis
Marleen Van Troys
Ghent University · BEAlbert Einstein College of Medicine · USUniversité Libre de Bruxelles · BEUniversity Medical Center Utrecht · NL

Funding

STRUCTUREU54GM064346 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI IMPERIALI, BARBARA · 2001 to 2010
$74.9M
SIGNAL TRANSDUCTION AND ACTIN DURING AMOEBOID CHEMOTAXISR01GM038511 · NIGMS · YESHIVA UNIVERSITY · PI CONDEELIS, JOHN S · 1988 to 2008
$2.8M
NIGMS NIH HHS GM-38511NIGMS NIH HHS R01 GM038511NIGMS NIH HHS U54 GM064346NIGMS NIH HHS U54GM064346
6 · The paper itself

Abstract

Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.

Indexed as

ActinsAnimalsCell MembraneCell MovementCell ShapeCofilin 1HumansMiceNIH 3T3 CellsPhosphatidylinositol 4,5-DiphosphatePseudopodiaRabbitsRecombinant Fusion ProteinsActinsCofilin 1Phosphatidylinositol 4,5-DiphosphateRecombinant Fusion Proteins

Identifiers

PMID19741095
PMCPMC2770939
OpenAlexW2136021967

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.