ArticleMolecular biology of the cell2009
Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge.
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 91 papers.
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Who cites it
91 citing papers in PubMed, 149 citations in OpenAlex.
- Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling.Nature cell biology · 2026Article
- Paclitaxel induces NM2-dependent cellular contraction through GEF-H1 dissociation from microtubules and RhoA/ROCK activation in cancer cells.Molecular oncology · 2026Article
- Obscurin a localizes near the cell membrane to modulate stress fiber dynamics and cell migration.The Journal of biological chemistry · 2026Article
- Ubiquitylation-dependent Rap2 activation regulates lamellipodia dynamics during cell migration.Journal of cell science · 2025Article
- Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration.Science advances · 2025Article
- MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio.eLife · 2025Article
- Dynamic Coupling of MAPK Signaling to the Guanine Nucleotide Exchange Factor GEF-H1.OncoTargets and therapy · 2025Review
- Keratinocyte-derived VEGF-A is an essential pro-migratory autocrine mediator, acting through the KDR/GEF-H1/RhoA pathway.Frontiers in cell and developmental biology · 2025Article
- Intracellular Signaling Pathways and Their Potential Targeting for Treatment of Ocular Posterior Segment Fibrosis.Journal of ophthalmic & vision research · 2025Review
- Compression-dependent microtubule reinforcement enables cells to navigate confined environments.Nature cell biology · 2024Article
- Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.Science advances · 2024Article
- CCDC88B interacts with RASAL3 and ARHGEF2 and regulates dendritic cell function in neuroinflammation and colitis.Communications biology · 2024Article
- Cdc42 activity in the trailing edge is required for persistent directional migration of keratinocytes.Molecular biology of the cell · 2024Article
- Fidgetin-like 2 depletion enhances cell migration by regulating GEF-H1, RhoA, and FAK.Biophysical journal · 2023Article
- Optogenetic modulation of guanine nucleotide exchange factors of Ras superfamily proteins directly controls cell shape and movement.Frontiers in cell and developmental biology · 2023Article
- The emerging role of microtubules in invasion plasticity.Frontiers in oncology · 2023Review
- Construction of a combined random forest and artificial neural network diagnosis model to screening potential biomarker for hepatoblastoma.Pediatric surgery international · 2022Article
- Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease.Cells · 2022Article
- Paxillin promotes breast tumor collective cell invasion through maintenance of adherens junction integrity.Molecular biology of the cell · 2022Article
- Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
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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Registered trials
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.