ArticleMolecular biology of the cell2010
Arp2/3- and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 102 citations in OpenAlex.
- Trial
- Relaxin-2: Shaping the Proteomic Landscape of Skeletal Muscle Physiology, Glucose Trafficking, and Mitochondrial Function in Rat.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Thromboxane signalling links immune activation to enhanced glucose uptake in skeletal muscle.Diabetologia · 2026Article
- Roles of DRP1 and the fission protein interactome as regulators of cellular stability and sarcopenia in skeletal muscle aging.Aging advances · 2025Article
- The Umbelliprenin-CTAB cellulose nanocrystal delivery system prevents hyperglycemia in diabetic rats by activating the insulin receptor IR/PDK1 pathway.Scientific reports · 2025Article
- The insulin signalling network.Nature metabolism · 2025Review
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- RAS-Related C3 Botulinum Toxin Substrate 1 Inhibition Attenuates Platelet Chemokine Activation in Diabetes Mellitus.Archives of Razi Institute · 2025Article
- Focal Adhesion Kinase Orchestrates GLUT4 Translocation and Glucose Uptake via Cytoskeletal Turnover in Primary Adipocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Coronary cytoskeletal modulation of coronary blood flow in the presence and absence of type 2 diabetes: the role of cofilin.Frontiers in physiology · 2025Article
- MicroRNA, Myostatin, and Metabolic Rate Depression: Skeletal Muscle Atrophy Resistance in HibernatingCells · 2024Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin.International journal of molecular sciences · 2023Article
- The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insulin signalling and GLUT4 trafficking in insulin resistance.Biochemical Society transactions · 2023Review
- Involvement of the extracellular matrix and integrin signalling proteins in skeletal muscle glucose uptake.The Journal of physiology · 2022Review
- Post-translational Modifications: The Signals at the Intersection of Exercise, Glucose Uptake, and Insulin Sensitivity.Endocrine reviews · 2022Review
- Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis.Frontiers in endocrinology · 2022Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
GLUT4 vesicles are actively recruited to the muscle cell surface upon insulin stimulation. Key to this process is Rac-dependent reorganization of filamentous actin beneath the plasma membrane, but the underlying molecular mechanisms have yet to be elucidated. Using L6 rat skeletal myoblasts stably expressing myc-tagged GLUT4, we found that Arp2/3, acting downstream of Rac GTPase, is responsible for the cortical actin polymerization evoked by insulin. siRNA-mediated silencing of either Arp3 or p34 subunits of the Arp2/3 complex abrogated actin remodeling and impaired GLUT4 translocation. Insulin also led to dephosphorylation of the actin-severing protein cofilin on Ser-3, mediated by the phosphatase slingshot. Cofilin dephosphorylation was prevented by strategies depolymerizing remodeled actin (latrunculin B or p34 silencing), suggesting that accumulation of polymerized actin drives severing to enact a dynamic actin cycling. Cofilin knockdown via siRNA caused overwhelming actin polymerization that subsequently inhibited GLUT4 translocation. This inhibition was relieved by reexpressing Xenopus wild-type cofilin-GFP but not the S3E-cofilin-GFP mutant that emulates permanent phosphorylation. Transferrin recycling was not affected by depleting Arp2/3 or cofilin. These results suggest that cofilin dephosphorylation is required for GLUT4 translocation. We propose that Arp2/3 and cofilin coordinate a dynamic cycle of actin branching and severing at the cell cortex, essential for insulin-mediated GLUT4 translocation in muscle cells.
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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 Socratic graph.