ArticleProceedings of the National Academy of Sciences of the United States of America2012
Gadkin negatively regulates cell spreading and motility via sequestration of the actin-nucleating ARP2/3 complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- LncRNA CISTR-ACT regulates cell size in human and mouse by guiding FOSL2.Nature communications · 2025Article
- The role of actin cytoskeleton component Arp2/3 in inflammatory response.Frontiers in cell and developmental biology · 2025Review
- Disulfidptosis: a novel cell death modality induced by actin cytoskeleton collapse and a promising target for cancer therapeutics.Cell communication and signaling : CCS · 2024Review
- One-Pot Analytical Pipeline for Efficient and Sensitive Proteomic Analysis of Extracellular Vesicles.Journal of proteome research · 2023Article
- Nucleation, stabilization, and disassembly of branched actin networks.Trends in cell biology · 2022Review
- Molecular mechanism of Arp2/3 complex inhibition by Arpin.Nature communications · 2022Article
- Macropinocytosis and Cell Migration: Don't Drink and Drive….Sub-cellular biochemistry · 2022Article
- Actin filament debranching regulates cell polarity during cell migration and asymmetric cell division.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity.Frontiers in cell and developmental biology · 2021Article
- Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration.Communications biology · 2020Article
- Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus.EMBO reports · 2020Article
- Cellular and pathophysiological consequences of Arp2/3 complex inhibition: role of inhibitory proteins and pharmacological compounds.Cellular and molecular life sciences : CMLS · 2019Review
- CYRI/ Fam49 Proteins Represent a New Class of Rac1 Interactors.Communicative & integrative biology · 2019Article
- Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex.The EMBO journal · 2018Article
- Actin-Based Cell Protrusion in a 3D Matrix.Trends in cell biology · 2018Review
- Fam49/CYRI interacts with Rac1 and locally suppresses protrusions.Nature cell biology · 2018Article
- Upregulation of Arp2 expression is associated with the prognosis and prediction of lymph node metastasis in bladder urothelial carcinoma.Cancer management and research · 2018Article
- An Integrative Framework Reveals Signaling-to-Transcription Events in Toll-like Receptor Signaling.Cell reports · 2017Article
- Global treadmilling coordinates actin turnover and controls the size of actin networks.Nature reviews. Molecular cell biology · 2017Review
- Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin.Journal of molecular biology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Regulation of actin dynamics is key to many cell physiological processes, ranging from protrusion formation and control of cell shape to cellular motility, endocytosis, and vesicle movement. The actin-related protein (ARP)2/3 complex is a major actin nucleator organizing branched filament networks in lamellipodial protrusions and during cell migration downstream of nucleation-promoting factors (NPFs). Although many NPFs have been characterized in detail, only few ARP2/3 inhibitors are known. Here, we identify the trans-Golgi network (TGN)/endosomally localized adaptor protein (AP)-1-associated adaptor protein Gadkin as a negative regulator of ARP2/3 function. Loss of Gadkin is associated with a partial redistribution of ARP2/3 to the plasma membrane and with increased cell spreading and migration, phenotypes that depend on the presence of a functional ARP2/3 complex. Gadkin directly binds to ARP2/3 via a conserved tryptophan-based acidic cluster motif reminiscent of ARP2/3-binding sequences of NPFs but fails to facilitate ARP2/3-mediated actin assembly. Consistent with an inhibitory role of Gadkin on ARP2/3 function, ARP2/3 is found on motile Gadkin-containing endosomal vesicles under migration-inhibiting conditions from where it relocalizes to the plasma membrane following activation of NPFs. Together with the observation that Gadkin-mediated inhibition of cell spreading requires its binding to ARP2/3, these data indicate that Gadkin is a negative regulator of ARP2/3 function present on intracellular membranes.
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