ArticleJournal of cell science2013
Rac1 is deactivated at integrin activation sites through an IQGAP1-filamin-A-RacGAP1 pathway.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Luminescent sensing of conformational integrin activation in living cells.Cell reports · 2025Article
- The hGIDLife science alliance · 2024Article
- Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition.Journal of experimental & clinical cancer research : CR · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- Article
- EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation.Cell death & disease · 2022Article
- Identification of IQGAP1 as a SLC26A4 (Pendrin)-Binding Protein in the Kidney.Frontiers in molecular biosciences · 2022Article
- Review
- The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry.Nature communications · 2021Article
- Alteration of the late endocytic pathway in Charcot-Marie-Tooth type 2B disease.Cellular and molecular life sciences : CMLS · 2021Article
- NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration.Frontiers in cell and developmental biology · 2021Article
- The adaptor protein APPL2 controls glucose-stimulated insulin secretion via F-actin remodeling in pancreatic β-cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Genetic analysis of the molecular regulation of electric fields-guided glia migration.Scientific reports · 2020Article
- Rabgap1 promotes recycling of active β1 integrins to support effective cell migration.Journal of cell science · 2020Article
- Basement membrane ligands initiate distinct signalling networks to direct cell shape.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Molecular Tuning of Filamin A Activities in the Context of Adhesion and Migration.Frontiers in cell and developmental biology · 2020Review
- Automated cell tracking using StarDist and TrackMate.F1000Research · 2020Article
- Rho GTPase signaling complexes in cell migration and invasion.The Journal of cell biology · 2018Review
- Integrins Modulate T Cell Receptor Signaling by Constraining Actin Flow at the Immunological Synapse.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. Although the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analysis of activated integrin-associated complexes suggests filamin-A and IQ-motif-containing GTPase-activating protein 1 (IQGAP1) as candidates that link β1 integrin to Rac1. siRNA-mediated knockdown of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analysis of individual filamin-A, IQGAP1 and Rac1 pull-downs and biochemical analysis, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated that RacGAP1 is recruited to IQGAP1 and active β1 integrin, and that suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings suggest a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby coordinate directional cell 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.