Cited by 148Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsCellular transport and secretion

Guanine Nucleotide Exchange Factor-H1 Regulates Cell Migration via Localized Activation of RhoA at the Leading Edge

Open access
Nalbant, Perihan, Chang, Yuan-Chen, Birkenfeld, Jörg, Chang, Zee-Fen, Bokoch, Gary M.·2009·Molecular Biology of the Cell

Abstract

Cell migration involves the cooperative reorganization of the actin and microtubule cytoskeletons, as well as the turnover of cell–substrate adhesions, under the control of Rho family GTPases. RhoA is activated at the leading edge of motile cells by unknown mechanisms to control actin stress fiber assembly, contractility, and focal adhesion dynamics. The microtubule-associated guanine nucleotide exchange factor (GEF)-H1 activates RhoA when released from microtubules to initiate a RhoA/Rho kinase/myosin light chain signaling pathway that regulates cellular contractility. However, the contributions of activated GEF-H1 to coordination of cytoskeletal dynamics during cell migration are unknown. We show that small interfering RNA-induced GEF-H1 depletion leads to decreased HeLa cell directional migration due to the loss of the Rho exchange activity of GEF-H1. Analysis of RhoA activity by using a live cell biosensor revealed that GEF-H1 controls localized activation of RhoA at the leading edge. The loss of GEF-H1 is associated with altered leading edge actin dynamics, as well as increased focal adhesion lifetimes. Tyrosine phosphorylation of focal adhesion kinase and paxillin at residues critical for the regulation of focal adhesion dynamics was diminished in the absence of GEF-H1/RhoA signaling. This study establishes GEF-H1 as a critical organizer of key structural and signaling components of cell migration through the localized regulation of RhoA activity at the cell leading edge.

Integrity signals

Registry

Crossref · 10.1091/mbc.e09-01-0041

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • GEF-H1 can control RhoA activity in response to local changes in the density of dynamic microtubules near the cell margin, e.g., to promote cell invasion or trigger cell retraction and help migrating dendritic cells maintain coherence.

    “In this way, GEF-H1 can control RhoA activity in response to local changes in the density of dynamic microtubules near the cell margin, for example, to promote cell invasion into a dense matrix or trigger cell retraction and help cells with long and elaborate protrusions, such as migrating dendritic cells, to maintain their coherence 21,24-26 .”

Cites

Flagged first, then by citations

1 of the 60 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Nalbant, P., Chang, Y.-C., Birkenfeld, J., Chang, Z.-F., & Bokoch, G. M.
Affiliations
  • Scripps Research Institute (US)
  • National Taiwan University (TW)
Venue
Molecular Biology of the Cell
Published
2009-09-15
Volume
20
Issue
18
Pages
4070-4082
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2151712953
Cited by
148
References
60
Citations by year
2026: 6 · 2025: 10 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 18 · 2020: 4 · 2019: 9 · 2018: 3 · 2017: 11 · 2016: 8 · 2015: 7 · 2014: 16 · 2013: 13 · 2012: 16
FWCI
4.43
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM39434, R01GM039434)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
GEF-H1, RhoA, cell migration, leading edge, RhoA activation, focal adhesions, actin dynamics, focal adhesion kinase, paxillin, Rho kinase, myosin light chain, microtubules, directional migration, HeLa cells, cytoskeletal remodeling
MeSH terms
Formins, Actins, Cell Movement, Enzyme Activation, HeLa Cells, Humans, Microtubules, Pseudopodia, Signal Transduction, Phosphotyrosine, Guanine Nucleotide Exchange Factors, rhoA GTP-Binding Protein, Focal Adhesions, Adaptor Proteins, Signal Transducing, Rho Guanine Nucleotide Exchange Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review