Evidence map›Paper›PMID 19013066›Full record

ArticleCurrent biology : CB2008

Symmetry-breaking polarization driven by a Cdc42p GEF-PAK complex.

Lukasz Kozubowski, Koji Saito, Jayme M Johnson, Audrey S Howell, Trevin R Zyla, Daniel J Lew

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

139 citing papers in PubMed, 254 citations in OpenAlex.

  1. Article
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  4. Role of Gα-MAPK interaction in mating ofMolecular biology of the cell · 2025
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  6. Review
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  9. Roles for the canonical polarity machinery in thebioRxiv : the preprint server for biology · 2025
    Article
  10. Article
  11. Septin Organization and Dynamics for Budding Yeast Cytokinesis.Journal of fungi (Basel, Switzerland) · 2024
    Review
  12. Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Mechanism of commitment to a mating partner inMolecular biology of the cell · 2022
    Article
  18. Orientation of Cell Polarity by Chemical Gradients.Annual review of biophysics · 2022
    Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Lukasz KozubowskiDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Koji Saito
Jayme M Johnson
Audrey S Howell
Trevin R Zyla
Daniel J Lew
Duke University · US

Funding

POLARITY ESTABLISHMENT IN YEASTR01GM062300 · NIGMS · DUKE UNIVERSITY · PI LEW, DANIEL J · 2001 to 2016
$5.0M
NIGMS NIH HHS GM62300NIGMS NIH HHS R01 GM062300
6 · The paper itself

Abstract

backgroundIn 1952, Alan Turing suggested that spatial patterns could arise from homogeneous starting conditions by feedback amplification of stochastic fluctuations. One example of such self-organization, called symmetry breaking, involves spontaneous cell polarization in the absence of spatial cues. The conserved GTPase Cdc42p is essential for both guided and spontaneous polarization, and in budding yeast cells Cdc42p concentrates at a single site (the presumptive bud site) at the cortex. Cdc42p concentrates at a random cortical site during symmetry breaking in a manner that requires the scaffold protein Bem1p. The mechanism whereby Bem1p promotes this polarization was unknown.

resultsHere we show that Bem1p promotes symmetry breaking by assembling a complex in which both a Cdc42p-directed guanine nucleotide exchange factor (GEF) and a Cdc42p effector p21-activated kinase (PAK) associate with Bem1p. Analysis of Bem1p mutants indicates that both GEF and PAK must bind to the same molecule of Bem1p, and a protein fusion linking the yeast GEF and PAK bypasses the need for Bem1p. Although mammalian cells lack a Bem1p ortholog, they contain more complex multidomain GEFs that in some cases can directly interact with PAKs, and we show that yeast containing an artificial GEF with similar architecture can break symmetry even without Bem1p.

conclusionsYeast symmetry-breaking polarization involves a GEF-PAK complex that binds GTP-Cdc42p via the PAK and promotes local Cdc42p GTP-loading via the GEF. By generating fresh GTP-Cdc42p near pre-existing GTP-Cdc42p, the complex amplifies clusters of GTP-Cdc42p at the cortex. Our findings provide mechanistic insight into an evolutionarily conserved pattern-forming positive-feedback pathway.

Indexed as

Cell PolarityAdaptor Proteins, Signal Transducingcdc42 GTP-Binding Protein, Saccharomyces cerevisiaeGuanine Nucleotide Exchange FactorsModels, BiologicalMutationp21-Activated KinasesProtein Structure, TertiaryRecombinant Fusion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAdaptor Proteins, Signal TransducingBEM1 protein, S cerevisiaecdc42 GTP-Binding Protein, Saccharomyces cerevisiaeGuanine Nucleotide Exchange Factorsp21-Activated KinasesRecombinant Fusion ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID19013066
PMCPMC2803100
OpenAlexW1978423927

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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.