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

The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.

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

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Nalbant, Perihan, Chang, Yuan-Chen, Birkenfeld, Jörg, Chang, Zee-Fen, Bokoch, Gary M.·2009·Molecular Biology of the Cell
DOI 10.1091/mbc.e09-01-0041PMC PMC2743625
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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.

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  1. Lim Y., 2008, J. Cell Biol, 180, 203
  2. Machacek M., 2009, Nature

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Metadata

Authors
Nalbant, P., Chang, Y.-C., Birkenfeld, J., Chang, Z.-F., & Bokoch, G. M.
Affiliations
  • Scripps Research Institute (US)
  • National Taiwan University (TW)
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2009-09-15
Volume
20
Issue
18
Pages
4070-4082
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e09-01-0041
PMC
PMC2743625
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

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