ArticleProceedings of the National Academy of Sciences of the United States of America2016
PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
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- A Rho GTPase-effector ensemble governs cell migration behavior.Nature communications · 2025Article
- PLEKHG2 and the PLEKHG family: Linking Rho family GTPases to neural development and disorders.Histology and histopathology · 2025Review
- Migratory responses in enucleated cells: The forces driving the locomotion movement of unicellular organisms.PNAS nexus · 2025Article
- An atlas of protein phosphorylation dynamics during interferon signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.The Journal of cell biology · 2024Article
- Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.Journal of cellular and molecular medicine · 2024Article
- Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024Review
- Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest.Nature cell biology · 2024Article
- Effects of highly active antiretroviral therapy initiation on epigenomic DNA methylation in persons living with HIV.Frontiers in bioinformatics · 2024Article
- Pathological and Therapeutic Significance of Tumor-Derived Extracellular Vesicles in Cancer Cell Migration and Metastasis.Cancers · 2023Review
- Orientation of Cell Polarity by Chemical Gradients.Annual review of biophysics · 2022Review
- PIPCommunications biology · 2022Article
- Transcription co-factor LBH is necessary for the survival of cochlear hair cells.Journal of cell science · 2021Article
- A hybrid stochastic-deterministic mechanochemical model of cell polarization.Molecular biology of the cell · 2020Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration.
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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.