Evidence map›Paper›PMID 25150978›Full record

ArticleNature cell biology2014

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

Matthew L Kutys, Kenneth M Yamada

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.9field-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

59 citing papers in PubMed, 87 citations in OpenAlex.

  1. Article
  2. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
    Review
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  9. Review of FRET biosensing and its application in biomolecular detection.American journal of translational research · 2023
    Review
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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 2 institutions in 1 country.

Matthew L KutysLaboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4370, USA.
Kenneth M YamadaLaboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4370, USA.
National Institute of Dental and Craniofacial Research · USNational Institutes of Health · US

Funding

Cell-Matrix Interactions and MigrationZIADE000524 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YAMADA, KENNETH · 2009 to 2025
$10.2M
Matrix Organization and DimensionalityZIADE000718 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YAMADA, KENNETH · 2009 to 2025
$8.9M
Intramural NIH HHS ZIA DE000524Intramural NIH HHS ZIA DE000718
6 · The paper itself

Abstract

Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

Indexed as

Cell Movementcdc42 GTP-Binding ProteinCell Line, TumorCell ShapeCollagenGTPase-Activating ProteinsHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsIntegrin alpha2beta1Protein Phosphatase 2Protein Processing, Post-TranslationalProtein Transportrac1 GTP-Binding ProteinrhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange Factorscdc42 GTP-Binding ProteinCollagenGTPase-Activating ProteinsIntegrin alpha2beta1Protein Phosphatase 2rac1 GTP-Binding ProteinRAC1 protein, humanrhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange FactorsSRGAP1 protein, human

Identifiers

PMID25150978
PMCPMC4150836
OpenAlexW1978792584

What OpenQuestion holds

Textmetadata
LicenceTDM
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.